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  • kinase
  • For replication to ensue, two protein kinases, cyclin-dependent kinase (Cdk)1p (also known as Cdc28p) and Cdc7p, must be activated. (genetics.org)
  • The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. (mdpi.com)
  • Myotonin-protein kinase (MT-PK) also known as myotonic dystrophy protein kinase (MDPK) or dystrophia myotonica protein kinase (DMK) is an enzyme that in humans is encoded by the DMPK gene. (wikipedia.org)
  • The dmpk gene product is a Ser/Thr protein kinase homologous to the MRCK p21-activated kinases and the Rho family of kinases. (wikipedia.org)
  • Myotonin-protein kinase is a serine-threonine kinase that is closely related to other kinases that interact with members of the Rho family of small GTPases. (wikipedia.org)
  • For example, myotonic dystrophy protein kinase has been shown to turn off (inhibit) part of a muscle protein called myosin phosphatase. (wikipedia.org)
  • Dystrophia myotonica protein kinase (DMPK) is a serine/threonine kinase composed of a kinase domain and a coiled-coil domain involved in the multimerization. (wikipedia.org)
  • The affinity of dimerisation suggested that the kinase domain alone is insufficient for dimerisation in vivo and that the coiled-coil domains are required for stable dimer formation. (wikipedia.org)
  • Myotonic dystrophy protein kinase has been shown to interact with HSPB2 and RAC1. (wikipedia.org)
  • In this model, transient activation of kinase activity would occur in response to G protein second messengers, while longterm activation of DMPK could be mediated by a membrane associated protease that cleaves DMPK-1 to release cytosolic DMPK-2 in a persistently activated form. (wikipedia.org)
  • Protein phosphorylation is a post-translational modification of proteins in which an amino acid residue is phosphorylated by a protein kinase by the addition of a covalently bound phosphate group. (wikipedia.org)
  • In the early 1980, the amino-acid sequence of the first protein kinase was determined which helped geneticists understand the functions of regulatory genes. (wikipedia.org)
  • In the late 1980s and early 1990s, the first protein tyrosine phosphatase (PTP1B) was purified and the discovery, as well as, cloning of JAK kinases was accomplished which led to many in the scientific community to name the 1990s as the decade of protein kinase cascades. (wikipedia.org)
  • transmembrane
  • Cystic fibrosis (CF) is a fatal autosomal-recessive genetic disorder caused by loss-of-function mutations in the CFTR gene, which encodes for the CFTR protein (CF transmembrane conductance regulator) ( 1 , 2 ). (pnas.org)
  • We earlier reported the BiHelix method for efficiently sampling the (12) 7 = 35 million conformations resulting from 30° rotations about the axis (η) of all seven transmembrane helices (TMHs), showing that the experimental structure is reliably selected as the best conformation from this ensemble. (pnas.org)
  • We find that the topologies of DM-20 and PLP are identical, with both proteins possessing four transmembrane domains and N and C termini exposed to the cytoplasm. (jneurosci.org)
  • We find that the transmembrane topologies of DM-20 and PLP are identical, with both proteins possessing four transmembrane domains and both N and C termini located within the cytoplasmic compartment. (jneurosci.org)
  • beta-hairpin
  • Blanco FJ, Rivas G, Serrano L. A short linear peptide that folds into a native stable beta-hairpin in aqueous solution. (springer.com)
  • A short linear peptide derived from the N-terminal sequence of ubiquitin folds into a water-stable non-native beta-hairpin. (springer.com)
  • As substitutions are the most common amino acid mutations, a protein could potentially undergo a conversion without affecting the functionality of the beta hairpin. (wikipedia.org)
  • In the folding of overall proteins, the turn may originate not in the native turn region but in the C-strand of the beta-hairpin. (wikipedia.org)
  • Sequences
  • However, the precise conformations of DM-20 and PLP may differ, because they each respond differently to many identical missense mutations in their primary sequences. (jneurosci.org)
  • Protein design involves identifying novel sequences within this subset. (wikipedia.org)
  • Thus, protein design is the search for sequences that have the chosen structure as a free energy minimum. (wikipedia.org)
  • interactions
  • 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)
  • Part of the protein folding problem is that several non-covalent, weak interactions are formed, such as hydrogen bonds and Van der Waals interactions. (wikipedia.org)
  • Rational protein design dates back to the mid-1970s, although initial protein design approaches were based mostly on sequence composition and did not account for specific interactions between side-chains at the atomic level. (wikipedia.org)
  • The conformation's name is derived from the idea that, in the absence of specific, stabilizing interactions, a polymer backbone will "sample" all possible conformations randomly. (wikipedia.org)
  • This is not actually the case, since the ensemble will be energy weighted due to interactions between amino acid side-chains, with lower-energy conformations being present more frequently. (wikipedia.org)
  • computational
  • The book ends with a synopsis the roles of computational biology and bioinformatics in protein science. (garlandscience.com)
  • Simulating protein folding motions is an important problem in computational biology. (biomedcentral.com)
  • The use of massive computational resources, such as tens of thousands of PCs in the Folding@Home project [ 5 , 6 ] have helped improve the time overhead involved but still are unable to handle very large proteins. (biomedcentral.com)
  • The solution to this paradox has been established by computational approaches to protein structure prediction. (wikipedia.org)
  • This is also described as protein folding directed within funnel-like energy landscapes Some computational approaches to protein structure prediction have sought to identify and simulate the mechanism of protein folding. (wikipedia.org)
  • Due to the development of computational protein design programs, and important successes in the field (see examples below), rational protein design has become one of the most important tools in protein engineering. (wikipedia.org)
  • Following the development of these computational tools, great success has been achieved over the last 30 years in protein design. (wikipedia.org)
  • Folding
  • Most patients with CF carry the F508del CFTR mutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in minimal amounts of CFTR at the cell surface. (pnas.org)
  • The F508del CFTR mutation impairs CFTR processing in the endoplasmic reticulum (ER) by preventing the protein from folding properly ( 12 - 14 ). (pnas.org)
  • This information can be relevant for understanding important areas of biology such as protein folding, protein aggregation and amyloid formation. (pubmedcentralcanada.ca)
  • The chaperonin containing TCP1 complex (CCT), also called TRiC or c-cpn, mediates protein folding in the cytosol. (biomedcentral.com)
  • Chaperonins are ATP-dependent protein-folding machines that are present in all kingdoms of life. (biomedcentral.com)
  • Kinetical accessibility: means that the path in the free energy surface from the unfolded to the folded state must be reasonably smooth or, in other words, that the folding of the chain must not involve highly complex changes in the shape (like knots or other high order conformations). (wikipedia.org)
  • How the protein reaches this structure is the subject of the field of protein folding, which has a related concept called Levinthal's paradox. (wikipedia.org)
  • Prions are stable conformations of proteins which differ from the native folding state. (wikipedia.org)
  • We present an algorithm that uses local learning to select appropriate connection methods in the context of roadmap construction for protein folding. (biomedcentral.com)
  • Knowledge of the stability, folding, kinetics, and detailed mechanics of the folding process may help provide insight into how and why the protein misfolds. (biomedcentral.com)
  • They construct a roadmap, or model, of the folding landscape by sampling conformations and connecting neighboring ones together with feasible transitions using a simple local planner. (biomedcentral.com)
  • Preliminary work applied connection learning to protein folding simulations [ 13 ], but with no way to ensure a good partitioning of the landscape, the results were only comparable to methods with no learning involved. (biomedcentral.com)
  • Correct protein folding is integral to proper functionality within biological systems. (wikipedia.org)
  • This is because protein folding requires entropic cost. (wikipedia.org)
  • Via several techniques, the mechanism of protein folding is currently being studied. (wikipedia.org)
  • Levinthal's paradox is a thought experiment, also constituting a self-reference in the theory of protein folding. (wikipedia.org)
  • If each of these bond angles can be in one of three stable conformations, the protein may misfold into a maximum of 3198 different conformations (including any possible folding redundancy). (wikipedia.org)
  • Indeed, the protein folding intermediates and the partially folded transition states were experimentally detected, which explains the fast protein folding. (wikipedia.org)
  • Chaperone - proteins that assist other proteins in folding or unfolding Folding funnel Anfinsen's dogma Levinthal, Cyrus (1969). (wikipedia.org)
  • The most important factor governing the folding of a protein into 3D structure is the distribution of polar and non-polar side chains. (wikipedia.org)
  • Folding of molecules, where some shapes are stable and functional, but others are not. (wikipedia.org)
  • Protein folding is the physical process by which a protein chain acquires its native 3-dimensional structure, a conformation that is usually biologically functional, in an expeditious and reproducible manner. (wikipedia.org)
  • The essential fact of folding, however, remains that the amino acid sequence of each protein contains the information that specifies both the native structure and the pathway to attain that state. (wikipedia.org)
  • Formation of a secondary structure is the first step in the folding process that a protein takes to assume its native structure. (wikipedia.org)
  • Functions
  • It is known that G-protein-coupled receptors exhibit several distinct low-energy conformations, each of which might favor binding to different ligands and/or lead to different downstream functions. (pnas.org)
  • Since being recognized in these three eukaryotic transcription factors, PAS domains have been found in proteins from all three kingdoms of life that perform functions as diverse as DNA binding, phosphorylation, ion conduction, and others ( , 1 ). (pnas.org)
  • Proteins perform extremely specific functions which are dependent on their structure. (wikipedia.org)
  • function
  • CFTR mutations that reduce CFTR protein function cause accumulation of thick, sticky mucus in the bronchi of the lungs, loss of exocrine pancreatic function, impaired intestinal secretion, and an increase in the concentration of chloride in the sweat ( 4 , 5 ). (pnas.org)
  • The book begins by introducing the basic principles of protein structure and function. (garlandscience.com)
  • Understanding the function of such proteins requires knowledge of the ensemble of low-energy configurations that might play a role in this pleiotropic functionality. (pnas.org)
  • The function of a protein depends on its? (memorize.com)
  • Proteins are stable enough to maintain a three-dimensional structure, but flexible enough for biological function. (wikipedia.org)
  • This β-sheet plays a particularly critical role in PAS structure and function because its solvent-exposed side is the binding site for a wide range of PAS-bound protein targets ( , 3 ). (pnas.org)
  • A protein domain is a conserved part of a given protein sequence and (tertiary) structure that can evolve, function, and exist independently of the rest of the protein chain. (wikipedia.org)
  • In a multidomain protein, each domain may fulfill its own function independently, or in a concerted manner with its neighbours. (wikipedia.org)
  • The main purpose of these models is to gain insights regarding the function of the flexible protein, extending the structure-function paradigm from folded proteins to intrinsically disordered proteins. (wikipedia.org)
  • Although the specific function of this protein is unknown, it appears to play an important role in muscle, heart, and brain cells. (wikipedia.org)
  • The sequence of a protein is unique to that protein, and defines the structure and function of the protein. (wikipedia.org)
  • Protein kinases and phosphatases work independently and in a balance to regulate the function of proteins. (wikipedia.org)
  • Secondary Structure
  • Some simple combinations of secondary structure elements have been found to frequently occur in protein structure and are referred to as supersecondary structure or motifs. (wikipedia.org)
  • structure
  • Both posttranslational modifications, phosphorylation and myristylation, contribute directly to the stable structure of this enzyme. (rcsb.org)
  • We have validated this method by predicting known crystal structure conformations starting from the template of a different protein structure. (pnas.org)
  • 3d structure of protein is determined by? (memorize.com)
  • Subsequent to the elucidation of the primary structure of PLP, several topologies for this protein have been proposed based on mathematical modeling, chemical labeling, limited protease digestion, and immunolabeling. (jneurosci.org)
  • A high-resolution solution structure of a mutant ARNT PAS-B domain stabilized in the new conformation revealed a 3-residue slip in register and accompanying inversion of the central Iβ-strand. (pnas.org)
  • This maintains the stability of the structure within localized segments of the protein. (wikipedia.org)
  • Each domain forms a compact three-dimensional structure and often can be independently stable and folded. (wikipedia.org)
  • One study has suggested that a single ancestral enzyme could have diverged into several families, while another suggests that a stable TIM-barrel structure has evolved through convergent evolution. (wikipedia.org)
  • The primary structure (string of amino acids) of a protein ultimately encodes its uniquely folded three-dimensional (3D) conformation. (wikipedia.org)
  • Proteins can be designed from scratch (de novo design) or by making calculated variants of a known protein structure and its sequence (termed protein redesign). (wikipedia.org)
  • In a sense, it is the reverse of protein structure prediction. (wikipedia.org)
  • When the first proteins were rationally designed during the 1970s and 1980s, the sequence for these was optimized manually based on analyses of other known proteins, the sequence composition, amino acid charges, and the geometry of the desired structure. (wikipedia.org)
  • Ensembles are models consisting of a set of conformations that together attempt to describe the structure of a flexible protein. (wikipedia.org)
  • This polypeptide lacks any stable (long-lasting) three-dimensional structure (the left hand side of the first figure). (wikipedia.org)
  • Amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein (the right hand side of the figure), known as the native state. (wikipedia.org)
  • Experiments beginning in the 1980s indicate the codon for an amino acid can also influence protein structure. (wikipedia.org)
  • The primary structure of a protein, its linear amino-acid sequence, determines its native conformation. (wikipedia.org)
  • Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. (wikipedia.org)
  • There are four distinct levels of protein structure. (wikipedia.org)
  • The primary structure of a protein refers to the sequence of amino acids in the polypeptide chain. (wikipedia.org)
  • The primary structure is held together by peptide bonds that are made during the process of protein biosynthesis. (wikipedia.org)
  • The primary structure of a protein is determined by the gene corresponding to the protein. (wikipedia.org)
  • enzyme
  • Plasma AFP, CCT3 and IQGAP3 protein levels were measured by enzyme linked immunosorbent assay (ELISA). (biomedcentral.com)
  • One is the lectin haemagglutinin protein with three relatively shallow sialic acid-binding sites and the other is enzyme sialidase with the active site in a pocket. (wikipedia.org)
  • The enzyme exists as a 415-residue monomer containing two nearly equal-sized domains that correspond to the N- and C-termini of the protein. (wikipedia.org)
  • polypeptide
  • 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 1969, Cyrus Levinthal noted that, because of the very large number of degrees of freedom in an unfolded polypeptide chain, the molecule has an astronomical number of possible conformations. (wikipedia.org)
  • amyloid fibrils
  • 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)
  • Several neurodegenerative and other diseases are believed to result from the accumulation of amyloid fibrils formed by misfolded proteins. (wikipedia.org)
  • affinity
  • It has been found that the affinity of peptide fragments of the human Pin1 WW domain for Cu(II) ions depends on its conformation. (springer.com)
  • Notably, some PAS domains control the binding affinity of this interface via changes in the conformation or occupancy of environmentally sensitive cofactors bound on the opposite, internal side of the sheet. (pnas.org)
  • statistical
  • So, if each conformation has an equal probability or statistical weight, chains are much more likely to be ball-like than they are to be extended - a purely entropic effect. (wikipedia.org)
  • differ
  • However, various GPCRs differ sufficiently in the tilts of the TMHs that this method need not predict the optimum conformation starting from any other template. (pnas.org)
  • Surprisingly, the conformation (as opposed to topology) of DM-20 and PLP may differ, which has been inferred from the divergent effects that many missense mutations have on the intracellular trafficking of these two isoforms. (jneurosci.org)
  • mutations
  • The 35 amino acid cytoplasmic peptide in PLP, which distinguishes this protein from DM-20, imparts a sensitivity to mutations in extracellular domains. (jneurosci.org)
  • Although both conformations are present in equivalent quantities in the Y456T mutant, this can be shifted almost completely to either end point by additional mutations. (pnas.org)
  • regulatory
  • MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C -terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α binding decreases the residual fluctuation of the MK5 model. (mdpi.com)
  • Domains can either serve as modules for building up large assemblies such as virus particles or muscle fibres, or can provide specific catalytic or binding sites as found in enzymes or regulatory proteins. (wikipedia.org)
  • small
  • In the small HCC group, CCT3 and IQGAP3 protein had sensitivity of 76.6 and 74.5 %, respectively. (biomedcentral.com)
  • There is great hope that the design of new proteins, small and large, will have uses in biomedicine and bioengineering. (wikipedia.org)
  • The close relationship of DMPK to the Rho-kinases has led to speculation whether DMPK activity may be regulated in vivo by small G proteins, particularly of the Rho family. (wikipedia.org)