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| | <StructureSection load='5dqn' size='340' side='right'caption='[[5dqn]], [[Resolution|resolution]] 2.26Å' scene=''> | | <StructureSection load='5dqn' size='340' side='right'caption='[[5dqn]], [[Resolution|resolution]] 2.26Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dqn]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DQN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DQN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dqn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DQN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.262Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4apy|4apy]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cyp125, MSMEI_5834 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</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=5dqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dqn OCA], [https://pdbe.org/5dqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dqn RCSB], [https://www.ebi.ac.uk/pdbsum/5dqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dqn 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/Linalool_8-monooxygenase Linalool 8-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.151 1.14.13.151] </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=5dqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dqn OCA], [http://pdbe.org/5dqn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dqn RCSB], [http://www.ebi.ac.uk/pdbsum/5dqn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dqn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CP125_MYCS2 CP125_MYCS2] Involved in the utilization of cholesterol as the sole carbon and energy source by degrading the side chain. Primarily catalyzes the sequential oxidation of the terminal methyl of cholest-4-en-3-one into (25S)-26-hydroxycholest-4-en-3-one (alcohol), (25S)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the carboxylic acid (25S)-3-oxocholest-4-en-26-oate. Also able to sequentially oxidize cholesterol itself, not only cholest-4-en-3-one.<ref>PMID:23489718</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Linalool 8-monooxygenase]] | + | [[Category: Mycolicibacterium smegmatis MC2 155]] |
| - | [[Category: Mycs2]]
| + | [[Category: Frank DJ]] |
| - | [[Category: Frank, D J]] | + | [[Category: Ortiz de Montellano PJ]] |
| - | [[Category: Montellano, P J.Ortiz de]] | + | [[Category: Waddling CA]] |
| - | [[Category: Waddling, C A]] | + | |
| - | [[Category: Cholesterol metabolism]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
CP125_MYCS2 Involved in the utilization of cholesterol as the sole carbon and energy source by degrading the side chain. Primarily catalyzes the sequential oxidation of the terminal methyl of cholest-4-en-3-one into (25S)-26-hydroxycholest-4-en-3-one (alcohol), (25S)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the carboxylic acid (25S)-3-oxocholest-4-en-26-oate. Also able to sequentially oxidize cholesterol itself, not only cholest-4-en-3-one.[1]
Publication Abstract from PubMed
Mycobacterium tuberculosis (Mtb) and Mycobacterium smegmatis (Msmeg) can grow on cholesterol as the sole carbon source. In Mtb the utilization of cholesterol can be initiated by CYP125A1 or CYP142A1 and in Msmeg by the orthologous CYP125A3 and CYP142A2. Double knockout of the two enzymes in Mtb prevents its growth on cholesterol, but the double knockout of Msmeg is still able to grow, albeit at a slower rate. We report here that Msmeg has a third enzyme, CYP125A4, that also oxidizes cholesterol, although it has a much higher activity for the oxidation of 7alpha-hydroxycholesterol. The ability of Msmeg CYP125A4 (and Mtb CYP125A1) to oxidize 7alpha-hydroxycholesterol is due, at least in part, to the presence of a smaller amino acid side chain facing C-7 of the sterol substrate than in CYP125A3. The ability to oxidize 7-substituted steroids broadens the range of sterol carbon sources for growth, but even more importantly in Mtb, additional biological effects are possible due to the potent immunomodulatory activity of 7alpha,26-dihydroxycholesterol.
Cytochrome P450 125A4, the Third Cholesterol C-26 Hydroxylase from Mycobacterium smegmatis.,Frank DJ, Waddling CA, La M, Ortiz de Montellano PR Biochemistry. 2015 Nov 24;54(46):6909-16. doi: 10.1021/acs.biochem.5b01029. Epub , 2015 Nov 11. PMID:26522442[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Garcia-Fernandez E, Frank DJ, Galan B, Kells PM, Podust LM, Garcia JL, Ortiz de Montellano PR. A highly conserved mycobacterial cholesterol catabolic pathway. Environ Microbiol. 2013 Feb 19. doi: 10.1111/1462-2920.12108. PMID:23489718 doi:10.1111/1462-2920.12108
- ↑ Frank DJ, Waddling CA, La M, Ortiz de Montellano PR. Cytochrome P450 125A4, the Third Cholesterol C-26 Hydroxylase from Mycobacterium smegmatis. Biochemistry. 2015 Nov 24;54(46):6909-16. doi: 10.1021/acs.biochem.5b01029. Epub , 2015 Nov 11. PMID:26522442 doi:http://dx.doi.org/10.1021/acs.biochem.5b01029
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