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| | <StructureSection load='5eig' size='340' side='right'caption='[[5eig]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='5eig' size='340' side='right'caption='[[5eig]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5eig]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EIG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EIG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5eig]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EIG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EIG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5OW:(2~{S})-2-AZANYL-6-[[(~{Z})-~{C}-[2-METHYL-3-OXIDANYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]-~{N}-[(2~{R})-1-OXIDANYL-1-OXIDANYLIDENE-3-SULFANYL-PROPAN-2-YL]CARBONIMIDOYL]AMINO]HEXANOIC+ACID'>5OW</scene>, <scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5OW:(2~{S})-2-AZANYL-6-[[(~{Z})-~{C}-[2-METHYL-3-OXIDANYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]-~{N}-[(2~{R})-1-OXIDANYL-1-OXIDANYLIDENE-3-SULFANYL-PROPAN-2-YL]CARBONIMIDOYL]AMINO]HEXANOIC+ACID'>5OW</scene>, <scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5eig FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eig OCA], [https://pdbe.org/5eig PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eig RCSB], [https://www.ebi.ac.uk/pdbsum/5eig PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eig ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cystathionine_gamma-lyase Cystathionine gamma-lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.1 4.4.1.1] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5eig FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eig OCA], [http://pdbe.org/5eig PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eig RCSB], [http://www.ebi.ac.uk/pdbsum/5eig PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eig ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Defects in CTH are the cause of cystathioninuria (CSTNU) [MIM:[http://omim.org/entry/219500 219500]]. It is an autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.<ref>PMID:18476726</ref> <ref>PMID:12574942</ref> | + | [https://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN] Defects in CTH are the cause of cystathioninuria (CSTNU) [MIM:[https://omim.org/entry/219500 219500]. It is an autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.<ref>PMID:18476726</ref> <ref>PMID:12574942</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN]] Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.<ref>PMID:19261609</ref> <ref>PMID:22169477</ref> <ref>PMID:19019829</ref> | + | [https://www.uniprot.org/uniprot/CGL_HUMAN CGL_HUMAN] Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.<ref>PMID:19261609</ref> <ref>PMID:22169477</ref> <ref>PMID:19019829</ref> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cystathionine gamma-lyase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Yan, W]] | + | [[Category: Yan W]] |
| - | [[Category: Zhang, J]] | + | [[Category: Zhang J]] |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
Disease
CGL_HUMAN Defects in CTH are the cause of cystathioninuria (CSTNU) [MIM:219500. It is an autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.[1] [2]
Function
CGL_HUMAN Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.[3] [4] [5]
References
- ↑ Zhu W, Lin A, Banerjee R. Kinetic properties of polymorphic variants and pathogenic mutants in human cystathionine gamma-lyase. Biochemistry. 2008 Jun 10;47(23):6226-32. doi: 10.1021/bi800351a. Epub 2008 May, 14. PMID:18476726 doi:10.1021/bi800351a
- ↑ Wang J, Hegele RA. Genomic basis of cystathioninuria (MIM 219500) revealed by multiple mutations in cystathionine gamma-lyase (CTH). Hum Genet. 2003 Apr;112(4):404-8. Epub 2003 Feb 6. PMID:12574942 doi:10.1007/s00439-003-0906-8
- ↑ Chiku T, Padovani D, Zhu W, Singh S, Vitvitsky V, Banerjee R. H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia. J Biol Chem. 2009 Apr 24;284(17):11601-12. doi: 10.1074/jbc.M808026200. Epub 2009, Mar 4. PMID:19261609 doi:10.1074/jbc.M808026200
- ↑ Krishnan N, Fu C, Pappin DJ, Tonks NK. H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. PMID:22169477 doi:10.1126/scisignal.2002329
- ↑ Sun Q, Collins R, Huang S, Holmberg-Schiavone L, Anand GS, Tan CH, van-den-Berg S, Deng LW, Moore PK, Karlberg T, Sivaraman J. Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H(2)S. J Biol Chem. 2009 Jan 30;284(5):3076-85. Epub 2008 Nov 19. PMID:19019829 doi:http://dx.doi.org/10.1074/jbc.M805459200
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