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HydroxylationProlineProline OxidaseMixed Function OxygenasesCytochrome P-450 Enzyme SystemProcollagen-Proline DioxygenaseMicrosomes, LiverSteroid HydroxylasesPyrroline Carboxylate ReductasesAryl Hydrocarbon Hydroxylases1-Pyrroline-5-Carboxylate DehydrogenaseSteroid 16-alpha-HydroxylaseBiotransformationKineticsDebrisoquinMolecular Sequence DataAmino Acid SequenceCholestanetriol 26-MonooxygenaseHydroxyprolineMephenytoinAmino Acid Transport Systems, NeutralHydroxylysineSubstrate SpecificityCytochrome P-450 CYP3ADealkylationOxidoreductases, N-DemethylatingChromatography, High Pressure LiquidNADPH-Ferrihemoprotein ReductaseOxidation-ReductionCatalysisOxygenasesHypoxia-Inducible Factor-Proline DioxygenasesMicrosomesBenzopyrene HydroxylaseStereoisomerismCytochrome P-450 CYP1A2Cytochrome P-450 CYP2D6CholestanesPhenylalanine HydroxylaseKetoglutaric AcidsEstrogens, CatecholBenzoflavonesProcollagen-Lysine, 2-Oxoglutarate 5-DioxygenaseChlorzoxazoneAmino AcidsGlutamate-5-Semialdehyde DehydrogenaseCollagenLauric AcidsRecombinant ProteinsMass SpectrometryTroleandomycinGas Chromatography-Mass SpectrometryCholecalciferolNADPAzetidinecarboxylic AcidOxygenHypoxia-Inducible Factor 1, alpha SubunitMutationMolecular StructureHydroxybenzoatesSulfaphenazolePhosphotransferases (Carboxyl Group Acceptor)PhenylalaninePhenobarbitalEscherichia coliCholestanolsCamphor 5-MonooxygenaseModels, MolecularBase SequenceIsoenzymesAnkyrin RepeatLiverCoumarinsCamphorCytochrome P-450 CYP2E1Cloning, MolecularCatechol OxidaseCytochromes b5BupropionBetaineBinding SitesProtein ConformationAlkane 1-MonooxygenaseAroclorsNorbornanesMutagenesis, Site-DirectedMagnetic Resonance SpectroscopyAscorbic Acid4-Hydroxybenzoate-3-MonooxygenaseProtein Structure, TertiarySequence Homology, Amino AcidScurvyStructure-Activity RelationshipProadifenAlkanesSpectrophotometryButyrophenonesQuinidineHydroxysteroidsProtein Binding
ResiduesLysine hydroxylationDegree of hydroxylationHydroxyprolineCollagen synthesisInhibitionProteinProlyl 4-hydroxylaTyrosineAminoGlycosylationPhosphorylationKinaseEnzymeMembraneHydroxylaseHypoxiaStabilityDegradationSequenceProteinsFamilyCellProlylLysinePost-translational hydroxylationSpecific prolineMetabolicPhenylalanineSubunitsPosttranslationalOxygenRibosomalHydroxylasesSynthesisSubstratePeptideImpairmentCompoundsReactionsCrucialProcollagenGeneStepGroupsAgent
Residues8
  • Collagens are post-translationally modified by proline hydroxylase to form the hydroxyproline residues. (embl.de)
  • Under normoxic conditions, prolyl hydroxylases (PHDs) hydroxylate the cite-specific proline residues of HIF-1α in a reaction that uses O 2 as a substrate. (spandidos-publications.com)
  • VHL within the VHL:ElonginB:ElonginC:CUL2:RBX1 Complex binds HIF-alpha subunits that have hydroxylated proline residues (Cockman et al. (reactome.org)
  • The third difference is the very high proportion of proline residues in the sequence accounting for about one-third of the sequence. (springer.com)
  • Vitamin C plays a crucial role in collagen synthesis, as it is required for the hydroxylation of proline and lysine residues in the collagen molecule. (elementsofhealing.net)
  • Here we report that prolyl hydroxylase 3 (PHD3) interacts with nonmuscle actin in human cells and catalyzes hydroxylation of actin at proline residues 307 and 322. (johnshopkins.edu)
  • Prolyl 3-hydroxlase 1 (P3H1), 2 another member of the 2-oxo-glutarate-dependent dioxygenase family, catalyzes the post-translational 3-hydroxylation of certain proline residues in fibril-forming collagens. (documents.pub)
  • In addition to the substrate, hydroxylation of peptidyl prolyl and peptidyl lysyl residues, catalyzed by prolyl hydroxylase and lysyl hydroxylase of skin, skeletal muscle, and granulating wounds, requires molecular oxygen, ascorbate, Fe 2+ , and alpha-ketoglutarate. (medscape.com)
Lysine hydroxylation3
  • Proteins synthesized at the ER are subject to covalent modifications that include N- and O-glycosylation, disulfide bond formation, and in some cases, proline and lysine hydroxylation. (stanford.edu)
  • The influence of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on lysine hydroxylation and cross-link formation in rat bone, cartilage and skin collagen. (supp.ai)
  • For example, prolyl 4-hydroxylase catalyzes proline 4-hydroxyla- tion, a modification necessary for the secondary and tertiary structure of collagen (1, 2), and the lysyl hydroxylase isoen- zymes catalyze lysine hydroxylation, a modification essential for the formation of intermolecular cross-links in collagen (2- 4). (documents.pub)
Degree of hydroxylation2
  • These sites showed tissue speci- ficity in degree of hydroxylation and a pattern of D-periodic spacing. (documents.pub)
  • Research has provided evidence of differences between mammalian collagens, such as variations in amino acid composition, the degree of hydroxylation of proline and lysine, and the type and stability of intermolecular crosslinks [9]. (coek.info)
Hydroxyproline4
  • 8 h following single oral doses of the compounds was associated with significant losses of radiolabelled proline and 4-hydroxyproline from collagen during this period. (embl.de)
  • The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxyproline. (embl.de)
  • P4HA1, the alpha subunit of Prolyl hydroxylation (P4H), is an enzyme hydroxylates proline into 4-hydroxyproline of collagens and other proteins with the -X-Pro-Gly- sequences as collagens in the endoplasmic reticulum. (zsr.cc)
  • Two isomeric forms of hydroxyproline have been identified in collagenTrans-4-hydroxy-L-proline is found in type I and type III collagen, whereas higher amounts of trans-3-hydroxy-L-proline are found in type IV collagen. (medscape.com)
Collagen synthesis3
Inhibition6
  • Two compounds, Compound 1 (1,4-dihydrophenanthrolin-4-one-3-carboxylic acid) and Compound 5 [8-(N-butyl-N-ethylcarbamoyl)-1,4-dihydrophenathrolin-4-one-3-carboxylic acid], with comparable potencies in vivo, were chosen to investigate the effect of the inhibition of the hydroxylation of newly synthesized uterine collagen on the turnover of this protein in vivo. (embl.de)
  • Inhibition of hydroxylation by more than 50% for approx. (embl.de)
  • Taken with the present results, this suggests that the potential use of inhibitors of prolyl 4-hydroxylase to control excessive collagen deposition in pathological fibrosis may be limited by the need to maintain continuous inhibition of collagen hydroxylation so as to facilitate intracellular degradation of the accumulated protein. (embl.de)
  • Blocking PHD3 expression or catalytic activity by short hairpin RNA knockdown or pharmacological inhibition, respectively, decreased actin prolyl hydroxylation. (johnshopkins.edu)
  • The goal of this study was to (I) identify new targets of PHDs in the heart, (II) test whether inhibition of prolyl hydroxylation alters protein stability and (III) investigate biological consequences. (nih.gov)
  • Doxorubicin-induced inhibition of prolyl hydroxylation during collagen biosynthesis in human skin fibroblast cultures. (qxmd.com)
Protein4
  • To address whether prolyl hydroxylation influences protein stability and to transfer the results to human, we used a cell culture model of iPS cell-derived cardiomyocytes and Stable Isotopic Labeling with Amino Acids (SILAC). (nih.gov)
  • The biological process of addition of a hydroxy group to a protein amino acid is called Hydroxylation. (microbenotes.com)
  • Protein hydroxylation is one type of PTM that involves the conversion of -CH group into -COH group and these hydroxylated amino acids are involved in the regulation of some important factors called transcription factors. (microbenotes.com)
  • In RNA interference experiments, P3H2 protein synthesis was suppressed coordinately with prolyl 3-hydroxylation at Pro- 944, Pro-707, and the C-terminal GPP repeat of the pN 1(II) chain, but Pro-986 remained fully hydroxylated. (documents.pub)
Prolyl 4-hydroxyla2
  • Examples of a novel series of phenanthrolinones are shown to be potent competitive inhibitors of avian prolyl 4-hydroxylase, and of collagen hydroxylation, in embryonic chick tendon cells and human foreskin fibroblasts in vitro and in the oestradiol-stimulated rat uterus in vivo. (embl.de)
  • Cone snail prolyl-4-hydroxylase α-subunit sequences derived from transcriptomic data and mass spectrometric analysis of variable proline hydroxylation in C. amadis venom. (ncbs.res.in)
Tyrosine2
  • SBT6.1-mediated cleavage within the variable domain allows for continued passage of the partially processed precursors through the secretory pathway, and for subsequent post-translational modifications including tyrosine sulfation and proline hydroxylation within, and proteolytic maturation after exit from the Golgi. (elifesciences.org)
  • Other modifications included tyrosine chlorination and dichlorination, and hydroxylations of tyrosine, tryptophan, and proline. (aston.ac.uk)
Amino5
Glycosylation4
Phosphorylation1
Kinase2
  • Prolonged hypoxia promotes the activation of RIPK1 kinase by modulating its proline hydroxylation, independent of the TNFα-TNFR1 pathway. (nature.com)
  • pVHL suppresses kinase activity of Akt in a proline-hydroxylation-dependent manner. (musc.edu)
Enzyme3
  • In enzymology, a proline 3-hydroxylase (EC 1.14.11.28) is an enzyme that catalyzes the chemical reaction L-proline + 2-oxoglutarate + O2 ⇌ {\displaystyle \rightleftharpoons } cis-3-hydroxy-L-proline + succinate + CO2 The 3 substrates of this enzyme are L-proline, 2-oxoglutarate, and O2, whereas its 3 products are cis-3-hydroxy-L-proline, succinate, and CO2. (wikipedia.org)
  • The systematic name of this enzyme class is L-proline,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating). (wikipedia.org)
  • The P3H1 enzyme there- fore is required for the 3-hydroxylation of Pro-986 in the 1(I) chain of type I collagen (8, 10). (documents.pub)
Membrane1
Hydroxylase1
Hypoxia2
  • The prolyl hydroxylation of hypoxia-inducible factor 1α (HIF-1α) mediated by the EGLN-pVHL pathway represents a classic signalling mechanism that mediates cellular adaptation under hypoxia. (nature.com)
  • Our findings illustrate a key role of the EGLN-pVHL pathway in suppressing RIPK1 activation under normoxic conditions to promote cell survival and a model by which hypoxia promotes RIPK1 activation through modulating its proline hydroxylation to mediate cell death and inflammation in human diseases, independent of TNFR1. (nature.com)
Stability1
Degradation1
  • Prolyl hydroxylases (PHD) are oxygen-dependent enzymes which add OH groups to prolines on HIF-1α that targets it for degradation. (nih.gov)
Sequence1
  • Which of the P4Hs act on signaling peptides, and whether or not they differ in preference for proline in a certain sequence context is still unclear. (elifesciences.org)
Proteins1
  • Magnesium plays a key role in this activation through use as a co-factor in the vitamin D binding proteins as well as being required in the process of hydroxylation. (bodybuilding.com)
Family1
  • Anyway, such small glycosylated and proline-rich toxins are totally different from any other known snake peptide and form, as a consequence, a new family of peptides. (springer.com)
Cell1
Prolyl10
  • 27. Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. (nih.gov)
  • Prolyl hydroxylases (PHD) are oxygen-dependent enzymes which add OH groups to prolines on HIF-1α that targets it for degradation. (nih.gov)
  • The goal of this study was to (I) identify new targets of PHDs in the heart, (II) test whether inhibition of prolyl hydroxylation alters protein stability and (III) investigate biological consequences. (nih.gov)
  • To address whether prolyl hydroxylation influences protein stability and to transfer the results to human, we used a cell culture model of iPS cell-derived cardiomyocytes and Stable Isotopic Labeling with Amino Acids (SILAC). (nih.gov)
  • Blocking PHD3 expression or catalytic activity by short hairpin RNA knockdown or pharmacological inhibition, respectively, decreased actin prolyl hydroxylation. (elsevierpure.com)
  • As with its human and yeast homologs, OGFOD1 and Tpa1p, respectively, we identified Sud1 to catalyze prolyl-hydroxylation of the small ribosomal subunit protein RPS23. (ox.ac.uk)
  • Like OGFOD1, Sud1 catalyzes a single prolyl-hydroxylation of RPS23 in contrast to yeast Tpa1p, where Pro-64 dihydroxylation is observed. (ox.ac.uk)
  • Amino acid analysis of rColXVII-A and -C demonstrated prolyl and lysyl hydroxylation with ratios for hydroxyproline/proline of 0.4 and for hydroxylysine/lysine of 0.5. (uni-luebeck.de)
  • This grant investigates the role of HIF prolyl-hydroxylation in acute ischemic kidney injury. (grantome.com)
  • A mixed-function oxygenase that catalyzes the hydroxylation of a prolyl-glycyl containing peptide, usually in PROTOCOLLAGEN , to a hydroxyprolylglycyl-containing-peptide. (nih.gov)
Lysine5
Post-translational hydroxylation1
Specific proline1
  • Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. (thermofisher.com)
Metabolic2
  • PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin. (nih.gov)
  • In vitro studies using human liver microsomes showed that bromocriptine has a high affinity for CYP3A and hydroxylations at the proline ring of the cyclopeptide moiety constituted a main metabolic pathway. (nih.gov)
Phenylalanine1
Subunits1
  • Primary cells revealed one substitution severely impaired OGFOD1-dependent hydroxylation of a neighboring proline residue resulting in 40S ribosomal subunits that were blocked from polysome formation. (ox.ac.uk)
Posttranslational1
  • Hydroxylation is a key posttranslational modification of collagen that gives rise to distinctive signals in the ssNMR spectrum of collagen proteins. (nih.gov)
Oxygen2
Ribosomal1
  • Ribosomal protein hydroxylation is emerging as an important 2OG oxygenase catalyzed pathway, but its biological functions are unclear. (ox.ac.uk)
Hydroxylases2
  • Hydroxylation and hydroxylases are not to be confused with hydrolysis and hydrolases . (wikipedia.org)
  • In biochemistry , hydroxylation reactions are often facilitated by enzymes called hydroxylases . (wikipedia.org)
Synthesis1
Substrate1
  • He wanted to assay it by a tritiated substrate in the same way he d followed the conversion of trans-4-3H-l-proline to 4-OH-proline in the post-translational conversion of procollagen to collagen. (nih.gov)
Peptide1
Impairment1
Compounds1
  • Hydroxylation is important in detoxification since it converts lipophilic compounds into water-soluble ( hydrophilic ) products that are more readily removed by the kidneys or liver and excreted . (wikipedia.org)
Reactions1
Crucial1
  • Proline hydroxylation is crucial for collagen and extracellular matrix assembly as well as for assembly of other protein molecules that have collagen-like domains, including surfactants and complement. (nih.gov)
Procollagen1
  • [ 8 ] Normal secretion of procollagen molecules out of the cells requires a critical amount of trans-4-hydroxy-L-proline. (medscape.com)
Gene1
Step1
Groups2
Agent1