• We proposed that a cell theoretically could in principle synthezise a big number of forms of [ 2 H]labeled macromolecules with somewhat different structures and conformations, so that a cell could easily select a preferable one from al these species in a course of adaptation to 2 H 2 O, that is the best suitable namely for that conditions. (o8ode.ru)
  • It is possible also to assume, that the macromolecules realize the special mechanisms, which promote a stabilization of their structure in 2 H 2 O and the functional reorganization for best working in 2 Н 2 О. (o8ode.ru)
  • Large macromolecules, including proteins and their complexes, very often adopt multiple conformations. (biorxiv.org)
  • Large macromolecules, including proteins and their complexes, are intrinsically flexible, and this flexibility is often linked with their function. (biorxiv.org)
  • Various interior dynamics including self organization of macromolecules, protein conformation, movement of human thoracic diaphragm, formation of logarithmic spiral in nature were discussed in the light of potential energy of self gravity and kinetic energy of metabolic energy. (webmedcentral.com)
  • Most of the structure databases obtain the 3D structure of biological macromolecules from techniques like X-ray crystallography, NMR Spectroscopy, Small angle X-ray scattering, Electron microscopy etc. (amrita.edu)
  • Radiation can disrupt the structure of the DNA (and other macromolecules), thereby disrupting normal cell and organ functions. (cdc.gov)
  • In our present view, these areas are found for systems where several types of macromolecules (proteins, polysaccharides or polyelectrolytes) and/or amphiphiles interact to form a functional or destructive unit. (lu.se)
  • G protein-coupled receptors are transmembrane proteins that help to regulate a wide array of biological processes, which makes them important drug targets. (elifesciences.org)
  • A ) G protein-coupled receptors (GPCRs) are transmembrane proteins (bottom) that can be regulated by orthosteric ligands (such as acetylcholine or iperoxo) and positive allosteric modulators (PAMs). (elifesciences.org)
  • This new approach has been shown to preserve mobility and enzymatic activity of transmembrane proteins in the resulting nSLB. (lu.se)
  • In each case, the amino acid substitution only leads to small perturbations in the conformation of the protein. (ubc.ca)
  • However, when the adaptive process goes continuously during the many generation, the population of cells can use a special genetic mechanisms for the adaptation to 2 H 2 O. For example, mutations of geens can be resulted in amino acid replacements in molecules of proteins, which in turn could cause a formation of a new isoenzymes, and in the special cases - even the anomal working enzymes of a newer structure type. (o8ode.ru)
  • How does an amino acid sequence that is unfolded when it leaves the ribosome manage to fold properly into a highly ordered, lightning-fast enzyme or sturdy structural protein? (anl.gov)
  • Is it possible to change an amino acid within a protein but not affecting that protein's functions? (stackexchange.com)
  • Finally, to our knowledge, the presented structure-search machinery is the only one to permit arbitrary combinations of amino-acid-type constraints, secondary structure constraints, distance constraints, and sequence separation constraints. (biomedcentral.com)
  • X: any amino acid except Pro) present in newly synthesized protein in yeast and mammalian cells. (elifesciences.org)
  • Higher energy is needed to break the bond between amino acid chains in recombinant bromelain showing by the enthalpy recorded suggesting that recombinant bromelain has good protein structure and conformation compared to commercial. (iium.edu.my)
  • Background: Designing amino acid sequences that are stable in a given target structure amounts to maximizing a conditional probability. (lu.se)
  • At the ribosome, the processed mRNA is translated to produce proteins from amino acid units. (cdc.gov)
  • The ionizable amino acid side chains of proteins are usually located at the surface. (lu.se)
  • Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared with published spike ectodomain structures. (nih.gov)
  • Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. (cdc.gov)
  • In vitro kinetic assays with purified Lhp1 showed that it robustly accelerates refolding of the Tetrahymena ribozyme from a stable misfolded state to its catalytically active conformation, suggesting that Lhp1 indeed possesses broad RNA chaperone activity. (utexas.edu)
  • Hexokinase IV/D) activator that reversibly targets a allosteric site that is only exposed for binding in the glucose-bound GK conformation, but not in the unbound 'super-open' GK conformation or the GKRP- (GK Regulatory Protein) bound GK, and effectively stabilizes GK in an active conformation as well as prevents its interaction with and nuclear sequestration by GKRP, while exhibiting little effect against Hexokinase I/II/III. (sigmaaldrich.com)
  • Hydrophobic collapse is one of the main events necessary for reaching a protein's stable and functional conformation. (wikipedia.org)
  • Amyloid fibrils are primarily composed of beta sheets and the main chain dominates the protein's structure. (wikibooks.org)
  • Upon co-incubation of GSH-MDI reaction products with human albumin, MDI was rapidly transferred to specific lysines of albumin, and the protein's native conformation/charge was altered, based on electrophoretic mobility. (cdc.gov)
  • However, previous work by this team of researchers from the University of Notre Dame and The University of Chicago has shown that, contrary to popular belief, intrinsically disordered proteins, which sample a variety of conformational forms the way the autotransporter proteins do, can remain quite extended in water even if they have high ratios of hydrophobic to charged amino acids. (anl.gov)
  • begingroup$ @danieldelrey - There are proteins which are intrinsically disordered ( en.wikipedia.org/wiki/Intrinsically_disordered_proteins ) or that contain regions which are intrinsically disordered. (stackexchange.com)
  • This phenomenon can be explained if Cdcp4 has more than one essential function or, alternatively, if two mutant proteins assemble to form a functional complex. (ubc.ca)
  • Moreover, targeting protein functional motions bears a great potential to control and modulate proteins' activities and interactions in physio-pathological contexts. (biorxiv.org)
  • In a second paper published in the Nov. 8 online issue of the journal Physical Review Letters, the scientists offer a detailed description of their novel device, an advanced version of the "optical trap," which uses infrared light to trap and control the forces on a functional protein, allowing researchers to monitor the molecule's every move in real time. (sciencedaily.com)
  • The plasma membranes are composed of various different constituents, but among all, membrane proteins are unanimously accepted as one of the major structural and functional pillars of the plasma membranes by the scientific community. (uni-goettingen.de)
  • Partial hydrophobic collapse is an experimentally accepted model for the folding kinetics of many globular proteins, such as myoglobin, alpha-lactalbumin, barstar, and staphylococcal nuclease. (wikipedia.org)
  • Globular proteins that are thought to fold by hydrophobic collapse are particularly amenable to complementary computational and experimental study using phi value analysis. (wikipedia.org)
  • This is thought to make globular proteins stable and soluble in the watery environment of the cell. (anl.gov)
  • Correct protein folding is integral to proper functionality within biological systems. (wikipedia.org)
  • Proteins that do not fold correctly are nonfunctional and contribute nothing to a biological system. (wikipedia.org)
  • In this case, a native conformation does not have to be at the lowest energy trough of the diagram as shown, it must simply exist in its natural and kinetically accessible conformation in biological systems. (wikipedia.org)
  • The authors believe their work will provide important information toward understanding basic questions of protein folding and tests long-held theories about how this remarkable biological process works. (anl.gov)
  • Significance Statement Proteins perform their biological functions by changing their shapes and interacting with each other. (biorxiv.org)
  • Identifying the molecular states relevant to protein functioning is necessary for our understanding of biological processes. (biorxiv.org)
  • As a key biological building block, the stability and conformation of amides affect the structures of peptides and proteins as well as their biological function. (rwth-aachen.de)
  • In the Nature experiment, we carried out the highest-resolution measurement ever made of an individual protein," says Steven Block, professor of applied physics and of biological sciences. (sciencedaily.com)
  • RNAs with biological functions that depend on higher-order structures are vulnerable to forming inactive alternative structures. (utexas.edu)
  • EU Marie Curie Training Site on Surface and colloid technology-self-assembled structures of biological and technological relevance. (lu.se)
  • In this model, we do not consider the interactions of the peptide backbone as this maintains its stability in non-polar and polar environments as long as there is sufficient hydrogen bonding within the backbone, thus we will only consider the thermodynamic contributions of the side chains to protein stability. (wikipedia.org)
  • long range interactions within the protein molecule. (flashcardmachine.com)
  • Based on the structure of Cdc4p, possible models for interallelic complementation including interactions with partner proteins and the formation of a myosin complex with Cdc4p fulfilling the role of both an essential and regulatory light chain are proposed. (ubc.ca)
  • The simulations show conformational order due to hydrogen bonding and other interactions illustrative of protein secondary structure. (pnnl.gov)
  • These techniques provide valuable insights on proteins' functioning and interactions with their environment. (biorxiv.org)
  • Reversible protein aggregation typically results from weaker protein interactions. (wikibooks.org)
  • All or other nearby charged groups, the pKa shift of a buried pH-dependent properties of proteins are ultimately governed residue is dominated by the large electrostatic self-energy by the electrostatic interactions of ionizable side chains. (lu.se)
  • 2004). The effect of electrostatic interactions is usually polarization effects in the protein are subsumed in an quantified in terms of the shift, DpKa, of the pKa value of an apparent dielectric constant, eP. (lu.se)
  • The reason why Peter Lansbury and others used the term 'natively unfolded' for a-synuclein and other proteins, especially peptides, is that they do not exist, to a significant degree, in the same kind of stable structure that larger native proteins like myoglobin do. (alzforum.org)
  • Protein aggregation can be described as the fibrilization or formation of insoluble structures from completely or partially unfolded peptides [2] . (wikibooks.org)
  • The extraordinary stability against proteolytic degradation in presence of proteases and ability to generate stable helical secondary structures, such as, 14- 12- and alternate 10/12-helices, with as few as 4-6 amino acids are the two main reasons behind the booming entry of β-peptides into peptidomimetics. (uni-goettingen.de)
  • Amyloidosis is a disorder of protein folding in which normally soluble proteins undergo a conformational change and are deposited in the extracellular space in an abnormal fibrillar form. (medscape.com)
  • The Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum (ER) membrane that is required for secretion of soluble proteins and production of many membrane proteins. (biorxiv.org)
  • Hydrophobic collapse is a proposed process for the production of the 3-D conformation adopted by polypeptides and other molecules in polar solvents. (wikipedia.org)
  • Here we present near-atomic-resolution structures of the human Sec61 channel inhibited by a comprehensive panel of structurally distinct small molecules- cotransin, decatransin, apratoxin F, ipomoeassin F, mycolactone, cyclotriazadisulfonamide (CADA) and eeyarestatin I (ESI). (biorxiv.org)
  • The Sec61 complex also mediates membrane integration of many proteins, including most cell surface receptors and cell adhesion molecules. (biorxiv.org)
  • In the case of structure of symmetrical molecules in PDB entry, it includes only a single subunit of the complex. (amrita.edu)
  • Biologically, all the protein molecules have hydrogen atom and all the bonds are satisfied to obtain a stable conformation. (amrita.edu)
  • Furthermore, one will need to be able to predict the structure patterns generated during the self-organization of whole layers of (bio)molecules on the surface. (degruyter.com)
  • But just as it had originally been the case in other fields of synthetic chemistry, such as molecular or solid state chemistry, the outcome of such a deposition with respect to the structure of the individual molecule or the structural arrangement of many molecules is very hard to predict without prior experimental input. (degruyter.com)
  • But we are still far away from an unbiased structure prediction of thermodynamically and/or kinetically stable structures of molecules on surfaces. (degruyter.com)
  • Similarly, the powerful global search techniques that have been applied to, and sometimes specifically developed for, the structure prediction of crystals and single molecules in vacuum or solvent can also be employed for the prediction of the structure(s) of molecules on surfaces. (degruyter.com)
  • The theory states that the nascent polypeptide forms initial secondary structure (ɑ-helices and β-strands) creating localized regions of predominantly hydrophobic residues. (wikipedia.org)
  • The team analyzed the cryogenic electron microscopy (cryo-EM) structure of the spike protein and chose substitutions that should make the structure more stable, such as additional disulfide bonds, salt bridges, proline residues, and hydrophobic residues that can fill internal cavities. (chemistryviews.org)
  • For example, changing a residue that resides on the outside of the protein from a positively charged one like Lysine to a positively charged one like Arginine (both residues are very similar) will not have any effect on the structure of the protein, in most cases. (stackexchange.com)
  • The possibility to define custom motifs and search for their occurrence in other proteins permits the identification of recurrent arrangements of residues that could have structural implications. (biomedcentral.com)
  • The extreme thermostability of PhAcP can be attributed to an extensive ion-pair network consisting of 13 charge residues on the beta sheet of the protein. (rcsb.org)
  • secreted PLA2s have also been found to specifically bind to a variety of soluble and membrane proteins in mammals, including receptors. (nih.gov)
  • The complex pharmacology of G-protein-coupled receptors (GPCRs) is defined by their multi-state conformational dynamics. (nature.com)
  • A complex interplay between structure, conformational dynamics and pharmacology defines distant regulation of G protein-coupled receptors. (elifesciences.org)
  • Allosteric regulation of G protein-coupled receptors. (elifesciences.org)
  • Activated receptors directly or indirectly regulate cellular biochemical processes (eg, ion conductance, protein phosphorylation, DNA transcription, enzymatic activity). (msdmanuals.com)
  • As other coronaviruses, 6-9 SARS-CoV-2 exploits host proteins to initiate cell-entry, in particular TMPRSS2 and ACE2, two membrane-bound proteins expressed in the upper and lower respiratory tract. (rsc.org)
  • While many studies have been focused on the membrane structure, the dynamics of such systems are crucial for the function of the membrane including membrane bound proteins. (lu.se)
  • The research of my laboratory is focused on nucleic acid enzymology, nucleic acid protein interaction and more recently on the development of modified human albumin for the treatment of shock. (utoledo.edu)
  • The rationale behind using polyethylene glycol-modified albumin is that this modified protein has a sufficiently large hydrodynamic radius that precludes its passing through defects in capillaries that occur in shock and is thus retained within blood vessels to maintain the oncotic gradient. (utoledo.edu)
  • To test this hypothesis, an occupationally relevant dose of MDI (0.1%w/v) was reacted with varying concentrations of GSH (10µM-10mM), and the reaction products were characterized with regard to mass/structure, and ability to carbamoylate human albumin, a major carrier protein for MDI in vivo. (cdc.gov)
  • The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position 414K, a preferred site of MDI reactivity on human albumin. (cdc.gov)
  • The 414K-MDI conjugation appears to covalently cross- link GSH to albumin via GSH's NH2-terminus, a unique conformation possibly resulting from cyclized mono(GSH)-MDI or asymmetric ( S , N -linked) bis(GSH)-MDI conjugates. (cdc.gov)
  • SARS-CoV-2 spike proteins that are stabilized in their prefusion configuration would, thus, be useful to improve protein yields. (chemistryviews.org)
  • Jennifer A. Maynard, Ilya J. Finkelstein, Jason S. McLellan, and colleagues, University of Texas, Austin, USA, have designed modified versions of the SARS-CoV-2 spike protein to find more stable variants that can be expressed at higher levels. (chemistryviews.org)
  • It has almost ten-fold higher expression than the parent spike protein, as well as increased thermostability. (chemistryviews.org)
  • The researchers determined the cryo-EM structure of HexaPro (pictured) with a resolution of 3.2 Å and found that it retains the prefusion spike conformation. (chemistryviews.org)
  • We performed cryo-election microscopy and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax, which is based on a full-length spike protein formulated in polysorbate 80 detergent. (nih.gov)
  • This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen. (nih.gov)
  • In vitro assays confirm that both drugs inhibit the human protein TMPRSS2, a SARS-Cov-2 spike protein activator. (rsc.org)
  • 10-13 TMPRSS2 contains an extracellular trypsin-like serine-protease domain that can proteolytically activate the spike (S) protein on the surface of SARS-CoV-2 viral particles 14 ( Fig. 1 ). (rsc.org)
  • Inclusion of MERS-spike protein ELISA in algorithm to determine serologic evidence of MERS-CoV infection. (cdc.gov)
  • However, despite huge efforts to optimize them, currently-used all-atom force fields are still not able, in a vast majority of cases, even to keep a protein molecule in its native conformation in the course of molecular dynamics simulations or to bring an approximate, homology-based model of protein structure closer to its native conformation. (nih.gov)
  • One cryoEM and over 50 high-resolution X-ray crystallographic structures are available for antagonist- or agonist-bound A 2A AR and for its ternary complex with an agonist and an engineered G protein, making this receptor an excellent model system for investigating GPCR structural dynamics. (nature.com)
  • While static structures provide critical information about the receptor's lowest energy states, our understanding of the A 2A AR function remains critically incomplete without detailed knowledge of its conformational dynamics. (nature.com)
  • We focus on the dynamics of the pseudorotation process, in particular, the lifetime of the THF conformations and their mutual rearrangements. (researchgate.net)
  • As no experimental structure is available, we provide a model of the TMPRSS2 equilibrium structure and its fluctuations by relaxing an initial homology structure with extensive 330 microseconds of all-atom molecular dynamics (MD) and Markov modeling. (rsc.org)
  • Understanding the molecular forces and other physico-chemical processes behind the folding conformation and transmembrane dynamics of these protein domains are an integral part in the process of developing updated synthetic transmembrane protein domains. (uni-goettingen.de)
  • by similarity, to similar proteins with structure having catalytic activity. (nih.gov)
  • The prediction of ligand binding or protein structure requires very accurate force field potentials - even small errors in force field potentials can make a 'wrong' structure (from the billions possible) more stable than the single, 'correct' one. (nih.gov)
  • In response to ligand binding, different A 2A AR amino acids either alter their sole stable conformations or vary relative probabilities of coexisting stable conformations 16 , 17 . (nature.com)
  • This pocket contracts around iperoxo, which results in iperoxo and the allosteric ligand forming a stable complex, but it does not contract around acetylcholine, which results in a more dynamic complex. (elifesciences.org)
  • Although several of the reported structures have been co-crystallized with L-Hcy pap-1-5-4-phenoxybutoxy-psoralen or methionine this doesn't influence the overall open conformation of the protein and all X-ray structures with folate analogs have so far been produced by soaking the ligand into preformed open-state crystals. (healthanddietblog.info)
  • Ligand-induced domain movement has been described for a reference set of 203 proteins that have been crystallized in more than one conformation and in the majority of cases (150) the ligand that initiates domain closure has contact with both domains [7]. (healthanddietblog.info)
  • This suggests that a closed MetE structure will only be obtained by co-crystallizing with a folate analog or other ligand that elicits the closed conformation. (healthanddietblog.info)
  • Cells depend on their DNA for coding information to make various classes of proteins that include enzymes, certain hormones, transport proteins, and structural proteins that support life. (cdc.gov)
  • The driving force behind protein folding is not well understood, hydrophobic collapse is a theory, one of many, that is thought to influence how a nascent polypeptide will fold into its native state. (wikipedia.org)
  • Hydrophobic collapse can be visualized as part of the folding funnel model which leads a protein to its lowest kinetically accessible energy state. (wikipedia.org)
  • The polypeptide will continue folding into lower energy states as long as these conformations are kinetically accessible. (wikipedia.org)
  • Protein Folding and Neurodegeneration: Biophysics to the Rescue? (alzforum.org)
  • This does not change our view of protein folding in the least. (alzforum.org)
  • Protein folding is one of the fascinating unanswered questions in biology. (anl.gov)
  • Autotransporter proteins then remain in an unfolded state in the periplasm until they pass through the outer bacterial membrane, folding properly along the way. (anl.gov)
  • This highly specialized protein folding process has attracted the attention of a team of researchers who have used this bacterial system as a model to determine what allows these unique proteins to maintain their disordered state in the periplasm. (anl.gov)
  • Current hypotheses on protein folding suggest that folding is initiated by formation of secondary structures followed by association of the hydrophobic regions of the emerging structure to orient them toward the interior of the protein in a process termed hydrophobic collapse. (anl.gov)
  • Going forward, the team will test the extent of collapse in an even wider range of sequences, to more fully understand the importance of maintaining a highly expanded conformation prior to folding. (anl.gov)
  • What influence does pH have on protein folding? (polygence.org)
  • The elucidation of the stable conformations and the folding process of proteins is one of the most fundamental and challenging goals in life science. (techconnect.org)
  • These RNA chaperone proteins are biologically critical, and they have long been hypothesized to possess nonspecific RNA binding as a general property - empowering a small collection of RNA chaperones to facilitate the folding of a large and diverse transcriptome. (utexas.edu)
  • Productive folding of the protein moiety is facilitated during this period by the calnexin/calreticulin cycle in mammalian cells, which relies on G1M9-specific lectin-type chaperones (calnexin and calreticulin) associated with the oxidoreductase ERp57, and UDP-glucose:glycoprotein glucosyltransferases 1 and 2, which are capable of re-adding glucose to M9 if the protein moiety is not yet folded. (elifesciences.org)
  • In order for us to understand protein aggregation, we need to understand more about protein folding in general. (wikibooks.org)
  • Advances have been made in understanding the protein folding process. (wikibooks.org)
  • The general folding process of a protein can be described as a "stochastic search" for the native state [3] [7] . (wikibooks.org)
  • 2018 ). Through YidC, proteins are inserted into the lipid bilayer via the SecYEG-dependent complex, but YidC functions as a chaperone in protein folding processes. (tcdb.org)
  • Parts derived from human and yeast proteins are outlined with solid and dashed lines, respectively. (biorxiv.org)
  • To identify new candidates for this nonspecific RNA chaperone activity, we performed affinity purifications of budding yeast RNA-binding proteins, using an exogenous and non-orthologous RNA as bait: the highly structured ribozyme derived from the Tetrahymena thermophila Group I intron. (utexas.edu)
  • From this pool of nonspecific RBPs, we selected the yeast La protein Lhp1 for further investigation. (utexas.edu)
  • Homologues of the yeast Oxa1 protein are found in chloroplasts of plants and in a wide variety of bacteria. (tcdb.org)
  • We model a protein as a network of atoms connected by springs and deform it along the least-energy directions. (biorxiv.org)
  • A Stanford University research team has designed the first microscope sensitive enough to track the real-time motion of a single protein down to the level of its individual atoms. (sciencedaily.com)
  • Electronic supplementary information (ESI) available: Protein coordinates and the point charges on all the atoms in the MM region (in PDB format) and the equilibrium geometries of the quantum region for all of the studied structures. (lu.se)
  • More than fifty years ago, Pauling and Corey described the two dominant forms of secondary structure, the α-helix and the β-sheet [ 1 ]. (biomedcentral.com)
  • This maintains the stability of the structure within localized segments of the protein. (wikipedia.org)
  • Then they combined the best-performing substitutions to further optimize the stability and expression of the protein. (chemistryviews.org)
  • Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. (bepress.com)
  • Recombinant bromelain is more stable than commercial bromelain at higher temperature but the stability reduced after 7 days of storage at 4oC. (iium.edu.my)
  • If two locally hydrophobic regions of two unrelated structures are left near each other in aqueous solution, aggregation will occur. (wikipedia.org)
  • See also David Thirumalai's Emerging Ideas on the Molecular Basis of Protein and Peptide Aggregation ' (.pdf). (alzforum.org)
  • Despite its deleterious impact on fitness, protein aggregation is a generic property of polypeptide chains, indissociable from protein structure and function. (uab.cat)
  • Protein aggregation is behind the onset of neurodegenerative disorders and one of the serious obstacles in the production of protein-based therapeutics. (uab.cat)
  • The development of computational tools opened a new avenue to rationalize this phenomenon, enabling prediction of the aggregation propensity of individual proteins as well as proteome-wide analysis. (uab.cat)
  • These studies spotted aggregation as a major force driving protein evolution. (uab.cat)
  • This toolbox allows to delineate conformation-specific routines to assist in the identification of aggregation-prone regions and to guide the optimization of more soluble and stable biotherapeutics. (uab.cat)
  • Here we review how the advent of predictive tools has change the way we think and address protein aggregation. (uab.cat)
  • Protein Aggregation has become a topic of growing interest in recent years, especially in pharmaceutical research. (wikibooks.org)
  • Protein aggregation is often encountered during late research stages or manufacturing of biopharma. (wikibooks.org)
  • Protein aggregation occurs when inter-chain contacts with other parts of that protein or other proteins. (wikibooks.org)
  • There are several diseases linked to protein aggregation. (wikibooks.org)
  • The reversibility of this type of aggregation can change when environmental factors such as protein concentration, salt concentration, or pH are varied [5] . (wikibooks.org)
  • The polypeptide interacts with water, thus placing thermodynamic pressures on these regions which then aggregate or "collapse" into a tertiary conformation with a hydrophobic core. (wikipedia.org)
  • In eukaryotes, secretory proteins are first translocated into the ER by the Sec61 complex before reaching the cell surface by vesicular trafficking. (biorxiv.org)
  • Mitochondrial TAT transports folded proteins in those eukaryotes with TatA and TatC subunits encoded in the mitochondrial genome. (tcdb.org)
  • 2007 ). Several Oxa1-type insertases in the ER serve as catalytically active core subunits in the ER membrane protein complex (EMC), the guided entry of tail-anchored (GET) and the GET- and EMC-like (GEL) complex. (tcdb.org)
  • DNA is often compared to a twisted ladder consisting of two strands connected by molecular rungs called "bases," which are known by the abbreviations A, T, G and C. Lengthier DNA sequences code for genes, which contain explicit instructions for building a specific protein. (sciencedaily.com)
  • With the help of cryo-electron microscopy, the recently awarded Nobel Prize winning method, researchers have now decoded the three-dimensional, molecular structure of the healthy human huntingtin protein. (mpg.de)
  • Now Rubén Fernández-Busnadiego from the Department of Molecular Structural Biology at the MPI of Biochemistry and Stefan Kochanek, head of the Department of Gene Therapy at the University Hospital Ulm, have succeeded in decoding the molecular, three-dimensional structure of the huntingtin protein. (mpg.de)
  • Fernández-Busnadiego, an expert in cryo-electron microscopy, mentions two main factors: 'First of all, cryo-electron microscopy has only been optimized in recent years to look at protein structures with almost molecular resolution. (mpg.de)
  • The three-dimensional molecular structure can be computed from the large number of resulting images. (mpg.de)
  • Proteins are the molecular machines of the cell. (mpg.de)
  • The crystal structure explains the mechanism of molecular assembly of the complex and reveals several acidic clusters at the interface responsible for association at low acidic pH and disassociation at basic/neutral pH. (nature.com)
  • The similarity of the general architecture between the PTC-E(M) and the previously determined PTC-A(M) strongly suggests that the progenitor M complexes of all botulinum serotypes may have similar molecular arrangement, although the neurotoxins apparently can take very different conformation when they are released from the M complex. (nature.com)
  • Although viewed as a constitutive housekeeping enzyme in the past, PP2A is a highly regulated phosphatase and is emerging as an important regulator of multiple cellular processes involving protein phosphorylation. (ac.be)
  • But advances in the understanding of protein phosphatases make now clear that these enzymes are precisely regulated and are as important as kinases in the regulation of cellular processes involving protein phosphorylation. (ac.be)
  • The lifetime of the drug-receptor complex is affected by dynamic processes (conformation changes) that control the rate of drug association and dissociation from the target. (msdmanuals.com)
  • We find that nafamostat has a higher MC population than camostat and GBPA, suggesting that nafamostat is more readily available to form the stable covalent enzyme-substrate intermediate, effectively explaining its high potency. (rsc.org)
  • Nouvelles avancées dans la structure et la régulation de la Protéine Phosphatase 2A : les raisons pour lesquelles PP2A ne doit plus être considérée comme une enzyme passive et non spécifique. (ac.be)
  • Les nouvelles avancées sur le sujet, particulièrement sur la structure et la régulation basée sur des modifications post-traductionnelles de PP2A, soulignent bien l'importance de la composition de l'holoenzyme PP2A dans les multiples rôles de cette enzyme majeure. (ac.be)
  • 2 Protein phosphatase 2A (PP2A) is a very abundant - it accounts for as much as 1% of total cellular proteins - ubiquitous and remarkably conserved enzyme. (ac.be)
  • 3 This article will review the recent advances in the structure and regulation of this fascinating enzyme. (ac.be)
  • In order to facilitate pap-1-5-4-phenoxybutoxy-psoralen the discovery of antifungal agents targeting the Met6p enzyme we have endeavored to crystallize and solve the X-ray structure of this key enzyme. (healthanddietblog.info)
  • We have been unable to crystallize the wild-type protein but here we report the use of surface entropy reduction SER [12 13 to produce three Met6p variants all with full enzyme activity that crystallized and allowed high resolution structures to be elucidated. (healthanddietblog.info)
  • Studies of the thermodynamics of binding of ligands to glycyl tRNAs suggest that the formation of glycyl adenylate, an obligate intermediate on the reaction pathway, is accompanied by a significant conformation change in the protein that alters the affinity of the enzyme for tRNA. (utoledo.edu)
  • Now that we know the exact structure of huntingtin, we can further study which areas of huntingtin are particularly important and how other proteins cooperate with huntingtin functionally. (mpg.de)
  • These functionally inappropriate proteins are somehow detected in the ER lumen and then transferred to the retrotranslocational channel embedded within the ER membrane, termed the retrotranslocon, followed by ubiquitin-dependent degradation by the proteasome in the cytoplasm. (elifesciences.org)
  • Today, recognition and classification of sequence motifs and protein folds is a mature field, thanks to the availability of numerous comprehensive and easy to use software packages and web-based services. (biomedcentral.com)
  • Hydrophobic collapse may also reduce the affinity of conformationally flexible drugs to their protein targets by reducing the net hydrophobic contribution to binding by self association of different parts of the drug while in solution. (wikipedia.org)
  • Conversely rigid scaffolds (also called privileged structures) that resist hydrophobic collapse may enhance drug affinity. (wikipedia.org)
  • The formation of amyloid fibrils, insoluble aggregates of hydrophobic protein can lead to a myriad of diseases including Parkinson's and Alzheimer's disease. (wikipedia.org)
  • The formation of a hydrophobic core requires the surface structures of this aggregate to maintain contact with both the polar solvent as well as the internal structures. (wikipedia.org)
  • This observation has led them to try and understand how proteins with high hydrophobic ratios can maintain these extended conformations. (anl.gov)
  • They found that swapping just 6 of the 334 amino acids (2%) in the N-terminal domain of pertactin to increase hydrophobic clustering was enough to induce significant contraction of the structure. (anl.gov)
  • This finding suggests that spacing of hydrophobic amino acids must be under selective pressure in bacterial proteins to facilitate their virulence functions. (anl.gov)
  • Familial renal amyloidosis (FRA) is a group of hereditary disorders in which misfolded proteins-amyloid-accumulate in the kidneys, causing proteinuria and/or hypertension followed by progressive kidney failure. (medscape.com)
  • The conditions that underlie amyloid deposition may be either acquired or hereditary, and at least 20 different proteins can form amyloid fibrils in vivo. (medscape.com)
  • The drawing depicts a generic amyloid fibril precursor protein (1) in equilibrium with a partially unfolded, molten, globulelike form of the protein (2) and its completely denatured state (3). (medscape.com)
  • [ 2 ] Research has shown that almost all patients with familial renal amyloidoses (FRA) are heterozygous for mutations in the genes for lysozyme, apolipoprotein AI, apolipoprotein AII, or fibrinogen A alpha-chain and that the amyloid fibrils in this condition are derived from the respective variant proteins. (medscape.com)
  • Their 3D structures (or potential attainable 3D structures, as in IDPs) are still responsible for the specific function e.g. binding to their specific substrate(s) or interacting partners. (stackexchange.com)
  • The larger Rep proteins, Rep78 and Rep68, assemble into stable, hexameric oligomers on specific secondary structures on the 3' and 5' termini of the single stranded viral DNA. (utoledo.edu)
  • Our studies are aimed at understanding how these proteins assemble on DNA structures and the specificity of their interaction with DNA. (utoledo.edu)
  • By using NMR spectroscopy, we demonstrate that purified Cdc4p is a monomeric protein with two structurally independent domains, each exhibiting a fold reminiscent of the EF-hand class of calcium-binding proteins. (ubc.ca)
  • A molecule in solution can be viewed as a structurally heterogeneous ensemble, where a finite number of conformational states ( e.g . active-inactive, bound-unbound) may become stable under certain conditions to perform specific tasks. (biorxiv.org)
  • In this paper, we describe an extension of DeepView/Swiss-PdbViewer through which structural motifs may be defined and searched for in large protein structure databases, and we show that common structural motifs involved in stabilizing protein folds are present in evolutionarily and structurally unrelated proteins, also in deeply buried locations which are not obviously related to protein function. (biomedcentral.com)
  • However, a 1.65 A crystal structure of the design described here turned out to be of a completely different fold: a four-helix, rodlike tetramer. (rcsb.org)
  • We attribute at least part of the discrepancy between the target fold and the crystal structure to the presence of a high concentration of dioxane. (rcsb.org)
  • The 1.5 A crystal structure of PhAcP adopts an alpha/beta sandwich fold that is common to other acylphosphatases. (rcsb.org)
  • Actual algorithms work on both protein sequences and structures, some of them accounting also for conformational fluctuations around the native state and the protein microenvironment. (uab.cat)
  • The native state of a protein that yields proper function is usually the most energetically favorable form of the protein at environmental conditions. (wikibooks.org)
  • The native state is usually a stable, low energy conformation. (wikibooks.org)
  • Nucleic acid having higher density finds place as 'core', medium denser protein in intermediate and least dense fat in the periphery. (webmedcentral.com)
  • A combination of fluorescence microscopy, neutron reflectometry, and time-of-flight secondary-ion mass spectrometry data will be presented which characterizes the structure and composition of this new supported lipid bilayer category. (lu.se)
  • Although acylphosphatase-like sequences are found in all three domains of life, no structure of acylphosphatase has been reported for bacteria and archaea so far. (rcsb.org)
  • Mitochondria import nuclearly-encoded proteins, made in the cell cytoplasm, into the mitochondrial matrix where their mitochondrial targeting sequences are removed by proteolysis. (tcdb.org)
  • Bacteria also export (to the periplasm) N-tails of membrane proteins synthesized without leader sequences by a Sec (Type IIPS)-independent mechanism. (tcdb.org)
  • A straightforward approach to accomplish this is a nested Monte Carlo where the conformation space is explored over and over again for different fixed sequences, which requires excessive computational demand. (lu.se)
  • Here, we report the characterization of enzymatic activities and crystal structure of an archaeal acylphosphatase. (rcsb.org)
  • To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. (bepress.com)
  • In the past, most of the attention was focused primarily on protein kinases and on their regulation, mainly because phosphatases were then viewed as simple housekeeping enzymes. (ac.be)
  • Aminoacyl tRNA synthetases are a class of enzymes that ensure the fidelity of protein synthesis by attaching amino acids to their cognate tRNAs. (utoledo.edu)
  • To get a clear picture, the researchers in the Kochanek lab have been looking for other proteins that interact with huntingtin and stabilize it. (mpg.de)
  • So the coordinates for quaternary structure of a protein should calculate from the coordinate of the subunit. (amrita.edu)
  • However, this conformation of the protein is difficult to produce by recombinant expression, i.e., using cells that have been modified with foreign DNA. (chemistryviews.org)
  • When we're taught biochemistry, we see proteins in their physiologically active forms. (alzforum.org)
  • Structural comparison to mesophilic acylphosphatases reveals significant differences in the conformation of the L5 loop connecting strands 4 and 5. (rcsb.org)
  • Our findings suggest that Lhp1 may rely on other proteins in vivo to rescue activity after cycles of duplex unwinding. (utexas.edu)
  • The main reason for our interest in general ( i.e. , sequentially non-contiguous) structural motifs, is the crucial role played by side-chains in the correct packing of proteins. (biomedcentral.com)
  • Most ionizable side chains reside at the protein surface, parent physical significance. (lu.se)
  • The system involves the study of what are termed autotransporter proteins, which pathogenic bacteria secrete as virulence factors for infection. (anl.gov)
  • This study tests the hypothesis that glutathione (GSH) reacts with MDI to form quasi-stable conjugates, capable of mediating the formation of MDI-conjugated "self" protein antigens, which may participate in pathogenic inflammatory responses. (cdc.gov)
  • However, the ongoing revolution in cryo-EM instrumentation ( 2 ) has supplied an exponentially growing body of near-atomic resolution structures. (biorxiv.org)
  • Hydrogen bonds between the carbonyl oxygen and the amido hydrogen four a.a. upstream, toward the C-Terminus of the helix, stabilize the helical structure. (flashcardmachine.com)
  • The structures indicate that Sec61 inhibitors stabilize the plug domain of Sec61 in a closed state, thereby preventing the protein-translocation pore from opening. (biorxiv.org)
  • Specialized cell structures called ribosomes are the cellular organelles that actually synthesize the proteins (RNA transcription). (cdc.gov)
  • Native membrane derived polymer-supported lipid bilayers (nSLBs) are poised to bridge the gap between live cell experiments and traditional model membrane architectures that by offering a combination of accessibility by surface sensitive analytical instrumentation and a composition which more closely resembles cellular membranes by displaying a diversity of endogenous membrane proteins, lipids, and carbohydrates. (lu.se)
  • In this review, we present an overview over the current state of the art regarding the prediction and clarification of structures of biomolecules on surfaces using theoretical and computational methods. (degruyter.com)
  • Side chain functionality, self-organizing conformations, and intermolecular self-assembly of TZPs may lead to biomimetic functionality and applications. (pnnl.gov)
  • Autoaggregation through the beta domains initiates fibril formation (4), providing a template for ongoing deposition of precursor proteins and for the development of the stable, mainly beta-sheet, core structure of the fibril (5). (medscape.com)
  • The protofibrils are composed of the cross-beta structure with the beta sheets running perpendicular to the fibril. (wikibooks.org)
  • Empirical rules and heuristics can be used to "explain" the structures observed after deposition. (degruyter.com)