• The substrate specificity of ABC transporters is determined by its associated substrate-binding proteins (SBPs). (nih.gov)
  • Multiple SBPs might broaden the substrate specificity by increasing the transporter capacity. (nih.gov)
  • Nudt16 is a member of the NUDIX family of hydrolases that show specificity towards substrates consisting of a ucleoside diphosphate linked to another moiety X. Several substrates for hNudt16 and various possible biological functions have been reported. (waw.pl)
  • However, some of these reports contradict each other and studies comparing the substrate specificity of the hNudt16 protein are limited. (waw.pl)
  • Protein phosphatase 2A (PP2A) is an enzymatic complex containing three subunits: a catalytic subunit, a scaffolding subunit, and one of several regulatory subunits responsible for dictating substrate specificity of the enzyme (42). (grandlacs-med-journal.com)
  • Structure is probed with vibrational spectroscopic tools that are capable of determining the Raman and IR spectra of bound substrates and specific protein molecular moieties embedded in large proteins. (elsevierpure.com)
  • While in periplasmic extracts of cells grown on glucose lower glucose binding activity was present compared to maltose binding activities Annotation of the complete genome sequence of T. maritima suggests that there may be at least two maltose binding proteins, MalE1 and MalE2, encoded in its genome. (uconn.edu)
  • The substrate specificities and affinities of substrate binding proteins MalE1 and MalE2 were measured and found to differ and are also expressed under different growth conditions. (uconn.edu)
  • Six other putative sugar binding proteins from examined and four of them were found to be binding to ribose, xylose, myo-inositol and digalacturonic acid with high affinities and specificities. (uconn.edu)
  • The IRS proteins (IRS1-4) are the family of adaptors regulating metabolic and mitogenic signaling pathways ( Hanke and Mann , 2009 Hanke S and Mann M (2009) The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. (scielo.br)
  • Following insulin binding, the insulin receptor (IR) autophosphorylates itself and creates docking sites for IRS proteins. (scielo.br)
  • The enzyme is structurally homologous to the NTP-binding kinase family of proteins but forms a solvent-accessible channel that binds to the donor substrate DMAPP, which is directed toward the acceptor substrate ATP/ADP. (tmu.edu.tw)
  • YfeA folds into a monomeric c-clamp like other substrate-binding proteins and has two metal-binding sites (sites 1 and 2). (uky.edu)
  • In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. (lu.se)
  • Regulated by guanine nucleotide exchange factors (GEFS) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (gaps) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. (lu.se)
  • Proteins that are chemically bound to a substrate material which renders their location fixed. (bvsalud.org)
  • In order to address this issue, we have examined the catalytically competent Fe(II)-loaded form of Pf MetAP-II ([Fe( Pf MetAP-II)]) in the absence and presence of both nitric oxide (NO) and the substrate-analogue inhibitor butaneboronic acid (BuBA) by kinetic and spectroscopic (EPR, UV−vis) methods. (bepress.com)
  • On the basis of these observations it is suggested that Cys-298 may form part of the 'S'-inhibitor binding site of the enzyme and may be responsible for tight binding of NADPH. (utmb.edu)
  • This inhibitor molecule blocks the active site so that the substrate has to compete with the inhibitor to attach to the enzyme. (medicalnewstoday.com)
  • This inhibitor binds to the enzyme and substrate. (medicalnewstoday.com)
  • This is an irreversible inhibitor, which binds to an enzyme and permanently inactivates it. (medicalnewstoday.com)
  • Molecular dynamics (MD) simulations highlight the improved stability for the substrate in the active site when ions are present, suggesting a binding order during the transport cycle. (elifesciences.org)
  • Our results reveal significant changes in dynamics in regions TM1, EL3, EL4, and TM12 upon binding co-transported ions (Na+/K+) and ligand-mediated changes in TM1, EL3 and EL4 upon binding 5-HT, the drugs S-citalopram, cocaine and ibogaine. (ku.dk)
  • Our results provide a comprehensive direct view of the conformational response of SERT upon binding both biologically relevant substrate/ions and ligands of pharmaceutical interest, thus advancing our understanding of the structure-function relationship in SERT. (ku.dk)
  • D) Coenzymes require additional ions to bind to enzymes but prosthetic groups are able to directly interact with enzymes. (biology-forums.com)
  • Some functionally important residues contributing to the formation of putative binding sites and permeation pathways for the cotransported Na+ ions and I- substrate were identified. (elsevierpure.com)
  • Xylose appears to be the optimal acceptor substrate for galactosylation by beta 4GalT7. (lu.se)
  • Integral membrane glutamate transporters couple the concentrative substrate transport to ion gradients. (biorxiv.org)
  • These transporters, many of which are sodium-coupled, have been shown to use an elevator mechanism of transport, but exactly how substrate binding is coupled to sodium ion binding and transport is not clear. (elifesciences.org)
  • The manuscript represents an important contribution to an ongoing discussion about the substrate binding site and mechanism of the Bile Acid Sodium Symporter (BASS) family of transporters. (elifesciences.org)
  • ii) do only homo-dimeric amino acid transporters contain two substrate binding sites or does this hold also for hetero-dimeric systems? (hu-berlin.de)
  • The energetics of the binding between murine ferrochelatase and mesoporphyrin were determined using isothermal titration calorimetry, which revealed a stoichiometry of one molecule of mesoporphyrin bound per protein monomer. (usf.edu)
  • This molecule binds to an enzyme somewhere other than the active site and reduces how effectively it works. (medicalnewstoday.com)
  • Accordingly, BIEs provide an experimental means of interrogating enzyme-substrate interactions and inform on the influence of enzyme-mediated atomic distortions in modulating substrate reactivity. (elsevierpure.com)
  • For chemokines binding with high affinity to sugar residues, immobilization can even lead to the formation of stable solid phase gradients, which induce a variant of haptotaxis 9 . (nature.com)
  • In previous structures of P2Ox, the substrate loop (residues 452-457) covering the active site has been either disordered or in a conformation incompatible with carbohydrate binding. (nih.gov)
  • To investigate the structural determinants of catalysis, covalent flavinylation, substrate binding, and regioselectivity, wild-type and mutant P2Ox enzymes were produced and characterized biochemically and structurally. (nih.gov)
  • B) Coenzymes are weakly bound whereas prosthetic groups are strongly bound to their respective enzymes. (biology-forums.com)
  • We have recently identified a new class of enzymes, Class IB, showing the acceptability of long (C20-C35) prenyl-diphosphates as substrates and no amino acid sequence homology with known TS. (elsevierpure.com)
  • A comparison of the primary deuterium kinetic isotope effect on the reduced and the carboxymethylated enzymes suggests that carboxymethylation did not affect the reaction sequence of substrate binding and release. (utmb.edu)
  • As both enzymes bind biphosphate substrates, each half barrel has a phosphate-binding motif, and HisF even exhibits limited HisA catalytic activity. (the-scientist.com)
  • The tentative determinant for discriminating between the two binding modes is the position of the O6 hydroxyl group, which in the C2-oxidation mode can make favorable interactions with Asp452 in the substrate loop and, possibly, a nearby arginine residue (Arg472). (nih.gov)
  • Ascorbate binding interactions are defined by the rsAPX/ascorbate crystal structure, which has been solved to 1.4 A (Chapter 3). (le.ac.uk)
  • Nucleobase stabilization by Π stacking interactions with His24 has been associated with strong binding of hNudt16 substrates. (waw.pl)
  • Current investigations on the interactions of the binding protein HisJ and the HisQMP2 transporter during the transport cycle studied by EPR(DEER) spectroscopy will be continued. (hu-berlin.de)
  • The kinetics of ligand binding/release will be probed here. (elsevierpure.com)
  • Insulin receptor substrate (IRS) is an important ligand in the insulin response of human cells. (wikipedia.org)
  • Molecular docking of hNudt16-ligand binding inside the hNudt16 pocket revealed two binding modes for representative substrates. (waw.pl)
  • On the other hand, encapsulation of ligand inside the active site is achieved through the N-terminal domain (NTD) movement, whereas the C-terminal domain (CTD) of αGlyBP is identified to be rigid and postulated to be responsible for maintaining the interaction with the transmembrane domain (TMD) during substrate translocation. (rcsb.org)
  • The mechanistic data imply (i) that BesD may have evolved from a hydroxylase ancestor either relatively recently or under weak selective pressure for efficient chlorination and (ii) that acquisition of its activity may have involved the emergence of linkage between l-Lys binding and chloride coordination following the loss of the anionic protein -carboxylate iron ligand present in extant hydroxylases . (bvsalud.org)
  • IRS1 (see also Insulin receptor substrate 1) IRS2 (see also Insulin receptor substrate 2) IRS3P - a pseudogene IRS4 van der Geer P, Wiley S, Pawson T (1999). (wikipedia.org)
  • Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. (scielo.br)
  • In addition to binding to the insulin receptor, IRS1 also binds to and transmits signals from the receptors of prolactin, growth hormone (GH), leptin, vascular endothelial growth factor (VEGF), tropomyosin receptor kinase B (TrkB), anaplastic lymphoma kinase (ALK), insulin like growth factor (IGF1), and integrins ( Vuori and Ruoslathi , 1994 Vuori K and Ruoslahti E (1994) Association of insulin receptor substrate-1 with integrins. (scielo.br)
  • Thus, the insulin receptor binds IRS. (wikipedia.org)
  • Metz H, Busch SE, Hanke ML, Kargl J, Kim KH and Houghton M (2014) Insulin receptor substrate-1 regulates immune cell content in lung adenocarcinoma. (scielo.br)
  • Metz HE and Houghton AM (2011) Insulin receptor substrate regulation of phosphoinositide 3-kinase. (scielo.br)
  • Sesti G, Federici M, Hribal ML, Lauro D, Sbraccia P and Lauro R (2001) Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. (scielo.br)
  • Ma Z, Gibson SL, Byrne MA, Zhang J, White MF and Shaw LM (2006) Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor metastasis. (scielo.br)
  • Cell migration is mainly governed by adhesion of cells to substrates (other cells or connective tissue) and by extracellular signalling molecules acting as motogenic stimuli or directional guidance cues 2 . (nature.com)
  • abstract = "Using STD NMR experiments, we have studied the binding epitopes of p-nitrophenyl glycosides of sialic acid and analogs thereof when bound to Trypanosoma cruzi trans-sialidase (TSia). (uni-luebeck.de)
  • abstract = "The substrate-binding protein YfeA (also known as YPO2439 or y1897) is a polyspecific metal-binding protein that is crucial for nutrient acquisition and virulence in Yersinia pestis, the causative microbe of plague. (uky.edu)
  • Time-dependent NMR spectra yielded data on the rate of substrate hydrolysis in comparison to sialic acid transfer. (uni-luebeck.de)
  • Novel crystal structures of a homo-dimeric amino acid transporter (ArtI-Q2N2) in complex with two substrate molecules raise some important questions concerning the general mechanism of Type I importers: (i) are two substrate molecules required to trigger ATP hydrolysis in a homo-dimeric transporter? (hu-berlin.de)
  • Finally, by random mutagenesis, we hope to isolate suppressor mutations in HisJ/HisQM that allow homo-dimeric variants (HisM2P2 and HisQ2P2) to transport substrate coupled to ATP hydrolysis. (hu-berlin.de)
  • Nitric oxide and cyanide bound rsAPX crystal structures have also been solved to 2.0 A and are used to model the binding of hydrogen peroxide in APX (Chapter 2). (le.ac.uk)
  • Canonical ABC transport systems mediating the uptake of solutes in prokaryotes are composed of an extracytoplasmic solute binding protein, two pore-forming subunits and an ATPase dimer. (hu-berlin.de)
  • The motion(s) of TIM's catalytically important mobile loop in releasing bound ligands and the time course of TIM-substrate to TIM-product inner complex conversion will be investigated by laser induced T-jump relaxation spectroscopy over our time range. (elsevierpure.com)
  • We found that DppA2 shows the highest flexibility on substrate recognition and that DppA2 and DppA4 have a higher tendency to utilize tripeptides. (nih.gov)
  • By exploiting saturation transfer difference (STD) NMR spectroscopy, the structural requirements necessary for API substrate recognition and binding were identified, with the aim of designing new API inhibitors. (unimib.it)
  • The structure analysis revealed that the diphosphate part of the substrate is located around the two characteristic Asp-rich motifs, and the hydrophobic tail is accommodated in a unique hydrophobic long tunnel, where the C35 prenyl-diphosphate, the longest substrate of BalTS, can be accepted. (elsevierpure.com)
  • this alters the shape of the active site so that substrates cannot bind to it. (medicalnewstoday.com)
  • The authors conclude that after isooctane extraction rat liver microsomes cannot bind hexobarbital and produce a type-I difference spectrum. (cdc.gov)
  • It consists of 2 catalytic (C) trimers held together by 3 dimers of regulatory (R) subunit which is itself composed of an effector binding domain and a Zinc binding domain. (europa.eu)
  • In periplasm extracts of cells grown on maltose, low maltose-binding activity was present compared to glucose-binding activity. (uconn.edu)
  • MalE1 binds maltose (K d 24 ± 1 μM), maltotriose (K d 8 ± 0.5 nM), and β-(1 → 4)-mannotetraose (K d 38 ± 1 μM). (uconn.edu)
  • MalE2 binds maltose (K d 8.4 ± 1 μM), maltotriose (K d 11.5 ± 1.5 μM) and trehalose (K d 9.5 ± 1.0 μM). (uconn.edu)
  • This study reports crystal structures of an α-glycoside-binding protein (αGlyBP, ORF ID: TTHA0356 from Thermus thermophilus HB8) in complex with disaccharide α-glycosides namely trehalose (α-1,1), sucrose (α-1,2), maltose (α-1,4), palatinose (α-1,6) and glucose within a resolution range of 1.6-2.0 Å. (rcsb.org)
  • The rsAPX crystal structure has been solved to 1.8 A (Chapter 2) and provides a useful comparison for the substrate bound structures. (le.ac.uk)
  • These data define the aromatic binding site in rsAPX and, along with the other crystal structures, have been used to propose a mechanism for proton transfer (Chapter 4). (le.ac.uk)
  • This structure provides new rationalization of the unusual functional features of the related cytochrome c peroxidase enzyme, and a mechanism for electron transfer from the substrate to the heme has been prepared (Chapter 3). (le.ac.uk)
  • EPR data also indicate that an interaction between the bound NO- and BuBA occurs forming a complex that mimics an intermediate step between the Michaelis complex and the tetrahedral transition-state. (bepress.com)
  • Alginate sulfate (AlgSulf) mimics sGAGs and binds growth factors such as basic fibroblast growth factor (FGF-2). (materialsconferences.com)
  • The heavy chain is responsible for both receptor some species of the genus Clostridium, in particular, Clostridium binding via its C-terminal (CT) binding domain [4,5] (HC) and botulinum, C. butyricum, C. baratii, and C. argentinense. (cdc.gov)
  • Based on enzymatic studies, that is galactosylation and its inhibition, conformational analysis and molecular modeling using the crystal structure, we propose that the binding pocket of beta 4GalT7 is very narrow, with a precise set of important hydrogen bonds. (lu.se)
  • Within seconds of substrate binding, we observe perturbed helical packing of the extracellular half of the substrate-binding domain. (biorxiv.org)
  • Sulfated glycosaminoglycans (sGAGs) are vital molecules of the extracellular matrix (ECM) of the nervous system known to regulate proliferation, migration, and differentiation of neurons mainly through binding relevant growth factors. (materialsconferences.com)
  • A newer model, the induced-fit model, helps to account for reactions between substrates and active sites that are not exact fits. (medicalnewstoday.com)
  • X-ray crystallography, kinetics, spectroscopy and directed evolution have been used to define substrate binding in recombinant soybean cystolic ascorbate peroxidase (rsAPX), which catalyses the hydrogen peroxide-dependent oxidation of ascorbate in plants. (le.ac.uk)
  • Until recently, this was also the only system for which a (single) substrate binding site had been identified within the transmembrane domains. (hu-berlin.de)
  • After having captured antigen in non-lymphoid tissues, DCs migrate along immobilized gradients of the high affinity sugar-binding chemokine (C-C motif) ligand21 (CCL21) towards lymphatic vessels, from where they are flushed into the sinus of lymph nodes. (nature.com)
  • Therefore, we quantitatively compared the affinity of hNudt16 towards a set of previously published substrates, as well as identified novel potential substrates. (waw.pl)
  • A new identified substrate for hNudt16, GppG, which binds the enzyme with an affinity comparable to that of IDP, suggests another potential regulatory role of this protein. (waw.pl)
  • We present here the crystal structure of H167A in complex with a slow substrate, 2-fluoro-2-deoxy-D-glucose. (nih.gov)
  • Here, we solve the crystal structure at 2.3 Å of a transporter from Neisseria meningitidis (ASBT NM ) in complex with pantoate, a potential substrate of ASBT NM . (elifesciences.org)
  • Here, we report the crystal structure bound with a substrate surrogate and biochemical analysis of a Class IB TS, using the enzyme from Bacillus alcalophilus (BalTS). (elsevierpure.com)
  • An increase in b-AlgSulf n concentration results in higher FGF-2 and β -NGF binding as demonstrated by greater frequency and dissipation shifts measured with quartz crystal microbalance with dissipation monitoring (QCM-D). Primary neurons seeded on the 2D b-AlgSulf n films maintain high viability comparable to positive controls grown on poly-d-lysine. (materialsconferences.com)
  • IRS-1, for example, is an IRS protein that contains a phosphotyrosine binding-domain (PTB-domain). (wikipedia.org)
  • The PTB-domain binds the NPXY sequence. (wikipedia.org)
  • One study (PMID: 16177568) reported aberrant splicing of transcripts from this gene which results in removal of the cyclin binding domain only in human cancer cells, and reduction in gene expression was shown in colorectal cancers (PMID: 17982127).Multiple transcript variants encoding different isoforms have been found for this gene. (nih.gov)
  • For methionine aminopeptidases (MetAPs), the exact location of this nucleophile, as well as of the substrate, with respect to the active site metal ion is unknown. (bepress.com)
  • Similarly, murine ferrochelatase variants, in which the active site Glu-289 was replaced by either glutamine or alanine and, when purified, contained specifically-bound protoporphyrin, exhibited enhanced protein stability when compared with wild-type ferrochelatase. (usf.edu)
  • In this model, an enzyme's active site is a specific shape, and only the substrate will fit into it, like a lock and key. (medicalnewstoday.com)
  • In this model, the active site changes shape as it interacts with the substrate. (medicalnewstoday.com)
  • Progression to the haloferryl intermediate upon the addition of O2 does not trap the substrates in the active site and, in fact, markedly diminishes cooperativity between halide and l-Lys. (bvsalud.org)
  • Plasma membrane-associated small GTPase which cycles between an active GTP-bond and inactive GDP-bound state. (lu.se)
  • At equilibrium, we show subtle differences in tilts of protomers in the outward-facing state and configurations of the substrate-binding pocket. (biorxiv.org)
  • Equilibrium binding isotope effects (BIEs) report on the bond vibrational status of enzyme substrates in the Michaelis complex prior to the transition state and how they differ from the solution state. (elsevierpure.com)
  • Implementation of the rapid equilibrium dialysis approach is described in the context of our recent studies on the substrate bonding environment for the human protein lysine N-methyltransferase NSD2. (elsevierpure.com)
  • These observations reveal different configurations of site 2 that enable cooperative metal binding and demonstrate how site 2 is dynamic and freely available for inter-protein metal coordination. (uky.edu)
  • Here, we apply hydrogen-deuterium exchange mass spectrometry to probe the conformational dynamics of human SERT in the absence and presence of known substrates and targeted drugs. (ku.dk)
  • This proton transfer suggests that hydrogen bonding between ferrochelatase and mesoporphyrin is a key factor in the thermodynamics of the binding reaction. (usf.edu)
  • Halide , 2OG, and (lastly) O2 all coordinate directly to the cofactor to initiate its conversion to a cis-halo-oxo- iron (IV) (haloferryl) complex, which abstracts hydrogen (Hâ ¢) from the non-coordinating prime substrate to enable radicaloid carbon - halogen coupling. (bvsalud.org)
  • Through binding to the host membrane, the monomer oligomerizes to form a 232.4 kDa membrane-inserted heptamer. (nature.com)
  • Differentiation into Th1 depends on the presence of IFN-γ and IL-12, which bind to receptors on the surface of CD4 T cells 5 . (bvsalud.org)
  • Structural and biochemical analysis of a bacterial homolog, ASTBnm, in complex with its native substrate (not bile acids, but a vitamin A precursor, pantoate) show a new binding site that is consistent with classical proposals for elevator-type transport mechanisms. (elifesciences.org)
  • NO binds to [Fe( Pf MetAP−II)] with a K d of 200 μM forming an {FeNO}7 complex. (bepress.com)
  • The portion of an enzyme to which substrates bind is referred to as the A) substrate complex. (biology-forums.com)
  • Spectroscopic and kinetic techniques were used to show that guaiacol and SHA bind at the same site in APX. (le.ac.uk)
  • Site 2 is a bidentate surface site capable of binding Zn and Mn atoms and is a unique feature of YfeA. (uky.edu)
  • Furthermore, we will apply site-directed mutagenesis combined with ATPase and transport assays to study the functional consequences of inactivating one of two substrate binding sites in the Art(MP)2 transporter. (hu-berlin.de)
  • Complementary, we will analyse the functional consequences of introducing a second binding site (in HisQ) in the HisQMP2 transporter in addition to that proposed for HisM. (hu-berlin.de)
  • CTP and ATP bind competitively to the same R site. (europa.eu)
  • THe OTCase lost most of its homotropic cooperativity and gained anabolic activity when residue glutamic acid (Glu) 106, near the CP binding site, was replaced by alanine (Ala) or glycine (Gly). (europa.eu)
  • We observe that the pantoate binds, specifically, between the N-termini of two of the opposing helices in this cross-over region. (elifesciences.org)
  • In well-studied cases, the three nongaseous substrates must bind to activate the enzyme 's Fe(II) cofactor for efficient capture of O2. (bvsalud.org)
  • In a mutant form of Glt Ph , we demonstrate substrate binding heterogeneity in the outward-facing state, modulated by temperature and salts. (biorxiv.org)
  • https://docs.substrate.io/quick-start/modify-the-runtime/ and I get this error after it completes a bunch of the build. (stackoverflow.com)
  • I'm trying to follow this procedure https://docs.substrate.io/tutorials/build-a-blockchain/build-local-blockchain/#start-the-local-node to start the local node. (stackoverflow.com)
  • Extensive cryo-EM analysis of the fully bound mutant Glt Ph provides multiple potential explanations of heterogeneous substrate binding. (biorxiv.org)
  • The substrate spectrum of the SBPs was elucidated by complementation of a penta mutant, deficient of all five SBPs, with plasmids carrying individual SBPs. (nih.gov)
  • The effect on the hexobarbital binding spectrum of the preparations was investigated. (cdc.gov)
  • At hexobarbital concentrations of 12.5mM or higher a type-II binding spectrum was obtained. (cdc.gov)
  • After addition of 2OG, subsequent coordination of the halide to the cofactor and binding of cationic l-Lys near the cofactor are associated with strong heterotropic cooperativity. (bvsalud.org)
  • The BASS family, however, transports a wide array of substrates other than bile acids. (elifesciences.org)
  • The modeling was based on templates from the LeuT-fold protein family and was done with emphasis on the refinement of the substrate-ion binding pocket. (elsevierpure.com)