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| | <StructureSection load='6bpr' size='340' side='right'caption='[[6bpr]], [[Resolution|resolution]] 1.96Å' scene=''> | | <StructureSection load='6bpr' size='340' side='right'caption='[[6bpr]], [[Resolution|resolution]] 1.96Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bpr]] is a 1 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=6BPR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BPR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bpr]] is a 1 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=6BPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BPR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO:NITRIC+OXIDE'>NO</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]] 1.96Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=F2Y:3,5-DIFLUORO-L-TYROSINE'>F2Y</scene></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=F2Y:3,5-DIFLUORO-L-TYROSINE'>F2Y</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO:NITRIC+OXIDE'>NO</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">CDO1 ([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=6bpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bpr OCA], [https://pdbe.org/6bpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bpr RCSB], [https://www.ebi.ac.uk/pdbsum/6bpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bpr 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/Cysteine_dioxygenase Cysteine dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.20 1.13.11.20] </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=6bpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bpr OCA], [http://pdbe.org/6bpr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bpr RCSB], [http://www.ebi.ac.uk/pdbsum/6bpr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bpr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CDO1_HUMAN CDO1_HUMAN]] Initiates several important metabolic pathways related to pyruvate and several sulfurate compounds including sulfate, hypotaurine and taurine. Critical regulator of cellular cysteine concentrations. Has an important role in maintaining the hepatic concentation of intracellular free cysteine within a proper narrow range. | + | [https://www.uniprot.org/uniprot/CDO1_HUMAN CDO1_HUMAN] Initiates several important metabolic pathways related to pyruvate and several sulfurate compounds including sulfate, hypotaurine and taurine. Critical regulator of cellular cysteine concentrations. Has an important role in maintaining the hepatic concentation of intracellular free cysteine within a proper narrow range. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cysteine dioxygenase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Li, J]] | + | [[Category: Li J]] |
| - | [[Category: Liu, A]] | + | [[Category: Liu A]] |
| - | [[Category: Shin, I]] | + | [[Category: Shin I]] |
| - | [[Category: Cys-tyr cofactor]]
| + | |
| - | [[Category: Cysteine]]
| + | |
| - | [[Category: Iron]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Unnatural amino acid]]
| + | |
| Structural highlights
6bpr is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.96Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CDO1_HUMAN Initiates several important metabolic pathways related to pyruvate and several sulfurate compounds including sulfate, hypotaurine and taurine. Critical regulator of cellular cysteine concentrations. Has an important role in maintaining the hepatic concentation of intracellular free cysteine within a proper narrow range.
Publication Abstract from PubMed
Cysteine dioxygenase (CDO) is a non-heme iron enzyme that adds two oxygen atoms from dioxygen to the sulfur atom of L-cysteine. Adjacent to the iron site of mammalian CDO, a post-translationally generated Cys-Tyr cofactor is present, whose presence substantially enhances the oxygenase activity. The formation of the Cys-Tyr cofactor in CDO is an autocatalytic process, and it is challenging to study by traditional techniques because the crosslinking reaction is a side, uncoupled, single-turnover oxidation buried among multiple turnovers of L-cysteine oxygenation. Here, we take advantage of our recent success in obtaining a purely uncrosslinked human CDO due to site-specific incorporation 3,5-difluoro-L-tyrosine (F2-Tyr) at the crosslinking site through the genetic code expansion strategy. Using EPR spectroscopy, we show that nitric oxide (*NO), an oxygen surrogate, similarly binds to uncrosslinked F2-Tyr157 CDO as in wild-type human CDO. We determined X-ray crystal structures of uncrosslinked F2-Tyr157 CDO and mature wild-type CDO in complex with both L-cysteine and *NO. These structural data reveal that the active site cysteine (Cys93 in the human enzyme), rather than the generally expected tyrosine (i.e., Tyr157), is well aligned to be oxidized should the normal oxidation reaction uncouple. This structural-based understanding is further supported by a computational study with models built on the uncrosslinked ternary complex structure. Together, these results strongly suggest that the first target to oxidize during the iron-assisted Cys-Tyr cofactor biogenesis is Cys93. Based on these data, a plausible reaction mechanism implementing a cysteine radical involved in the crosslink formation is proposed.
Probing the Tyr-Cys Cofactor Biogenesis in Cysteine Dioxygenase by the Genetic Incorporation of Fluorotyrosine.,Li J, Koto T, Davis I, Liu A Biochemistry. 2019 Apr 4. doi: 10.1021/acs.biochem.9b00006. PMID:30946568[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li J, Koto T, Davis I, Liu A. Probing the Tyr-Cys Cofactor Biogenesis in Cysteine Dioxygenase by the Genetic Incorporation of Fluorotyrosine. Biochemistry. 2019 Apr 4. doi: 10.1021/acs.biochem.9b00006. PMID:30946568 doi:http://dx.doi.org/10.1021/acs.biochem.9b00006
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