|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Structure and kinetic analysis of H2S production by human Mercaptopyruvate Sulfurtransferase== | | ==Structure and kinetic analysis of H2S production by human Mercaptopyruvate Sulfurtransferase== |
| - | <StructureSection load='4jgt' size='340' side='right' caption='[[4jgt]], [[Resolution|resolution]] 2.16Å' scene=''> | + | <StructureSection load='4jgt' size='340' side='right'caption='[[4jgt]], [[Resolution|resolution]] 2.16Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jgt]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JGT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JGT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jgt]] is a 3 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=4JGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JGT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</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]] 2.161Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</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">MPST, TST2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4jgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jgt OCA], [https://pdbe.org/4jgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jgt RCSB], [https://www.ebi.ac.uk/pdbsum/4jgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jgt 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/3-mercaptopyruvate_sulfurtransferase 3-mercaptopyruvate sulfurtransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.1.2 2.8.1.2] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jgt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jgt RCSB], [http://www.ebi.ac.uk/pdbsum/4jgt PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/THTM_HUMAN THTM_HUMAN]] Encephalopathy due to beta-mercaptolactate-cysteine disulfiduria. Note=Aberrant MPST activity is found in a few cases of mercaptolactate-cysteine disulfiduria (MCDU) characterized by the appearance of large quantaties of the sulfur-containing amino acid, beta-mercaptolactate-cysteine disulfide, in the urine (PubMed:4973015, PubMed:4690911 and PubMed:6945862). Some cases have associated mental retardation (PubMed:4973015 and PubMed:6945862). | + | [https://www.uniprot.org/uniprot/THTM_HUMAN THTM_HUMAN] Encephalopathy due to beta-mercaptolactate-cysteine disulfiduria. Note=Aberrant MPST activity is found in a few cases of mercaptolactate-cysteine disulfiduria (MCDU) characterized by the appearance of large quantaties of the sulfur-containing amino acid, beta-mercaptolactate-cysteine disulfide, in the urine (PubMed:4973015, PubMed:4690911 and PubMed:6945862). Some cases have associated mental retardation (PubMed:4973015 and PubMed:6945862). |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/THTM_HUMAN THTM_HUMAN]] Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions (By similarity). | + | [https://www.uniprot.org/uniprot/THTM_HUMAN THTM_HUMAN] Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 20: |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4jgt" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| Line 28: |
Line 28: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3-mercaptopyruvate sulfurtransferase]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Banerjee, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Chiku, T]] | + | [[Category: Banerjee R]] |
| - | [[Category: Koutmos, M]] | + | [[Category: Chiku T]] |
| - | [[Category: Yadav, P K]] | + | [[Category: Koutmos M]] |
| - | [[Category: Yamada, K]] | + | [[Category: Yadav PK]] |
| - | [[Category: Rhodanese]]
| + | [[Category: Yamada K]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
THTM_HUMAN Encephalopathy due to beta-mercaptolactate-cysteine disulfiduria. Note=Aberrant MPST activity is found in a few cases of mercaptolactate-cysteine disulfiduria (MCDU) characterized by the appearance of large quantaties of the sulfur-containing amino acid, beta-mercaptolactate-cysteine disulfide, in the urine (PubMed:4973015, PubMed:4690911 and PubMed:6945862). Some cases have associated mental retardation (PubMed:4973015 and PubMed:6945862).
Function
THTM_HUMAN Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions (By similarity).
Publication Abstract from PubMed
Mercaptopyruvate sulfurtransferase (MST) is a source of endogenous H2S, a gaseous signaling molecule implicated in a wide range of physiological processes. The contribution of MST versus the other two H2S generators, cystathionine beta-synthase and gamma-cystathionase has been difficult to evaluate since many studies on MST have been conducted at high pH and have used varied reaction conditions. In this study, we have expressed, purified and crystallized human MST in the presence of the substrate, 3-mercaptopyruvate (3-MP). The kinetics of H2S production by MST from 3-MP was studied at pH 7.4 in the presence of various physiological persulfide acceptors: cysteine, dihydrolipoic acid, glutathione, homocysteine and thioredoxin and in the presence of cyanide. The crystal structure of MST reveals a mixture of the product complex containing pyruvate and an active site cysteine persulfide (Cys248-SSH), and a nonproductive intermediate in which 3-MP is covalently linked via a disulfide bond to an active site cysteine. The crystal structure analysis allows us to propose a detailed mechanism for MST in which an Asp-His-Ser catalytic triad is positioned to activate the nucleophilic cysteine residue and participate in general acid-base chemistry while our kinetic analysis indicates that thioredoxin is likely to be the major physiological persulfide acceptor for MST.
Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase.,Yadav PK, Yamada K, Chiku T, Koutmos M, Banerjee R J Biol Chem. 2013 May 22. PMID:23698001[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yadav PK, Yamada K, Chiku T, Koutmos M, Banerjee R. Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. J Biol Chem. 2013 May 22. PMID:23698001 doi:10.1074/jbc.M113.466177
|
