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2yoo

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Current revision

Cholest-4-en-3-one bound structure of CYP142 from Mycobacterium smegmatis

Structural highlights

2yoo is a 4 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.69Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CP142_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 (25R)-26-hydroxycholest-4-en-3-one (alcohol), (25R)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the carboxylic acid (25R)-3-oxocholest-4-en-26-oate. Also able to sequentially oxidize cholesterol itself, not only cholest-4-en-3-one.^[1] ^[2]

Publication Abstract from PubMed

Degradation of the cholesterol side-chain in Mycobacterium tuberculosis is initiated by two cytochromes P450, CYP125A1 and CYP142A1, that sequentially oxidize C26 to the alcohol, aldehyde and acid metabolites. Here we report characterization of the homologous enzymes CYP125A3 and CYP142A2 from Mycobacterium smegmatis mc2 155. Heterologously expressed, purified CYP125A3 and CYP142A2 bound cholesterol, 4-cholesten-3-one, and antifungal azole drugs. CYP125A3 or CYP142A2 reconstituted with spinach ferredoxin and ferredoxin reductase efficiently hydroxylated 4-cholesten-3-one to the C-26 alcohol and subsequently to the acid. The X-ray structures of both substrate-free CYP125A3 and CYP142A2 and of cholest-4-en-3-one-bound CYP142A2 reveal significant differences in the substrate binding sites compared with the homologous M. tuberculosis proteins. Deletion only of cyp125A3 causes a reduction of both the alcohol and acid metabolites and a strong induction of cyp142 at the mRNA and protein levels, indicating that CYP142A2 serves as a functionally redundant back up enzyme for CYP125A3. In contrast to M. tuberculosis, the M. smegmatis Deltacyp125Deltacyp142 double mutant retains its ability to grow on cholesterol albeit with a diminished capacity, indicating an additional level of redundancy within its genome.

A highly conserved mycobacterial cholesterol catabolic pathway.,Garcia-Fernandez E, Frank DJ, Galan B, Kells PM, Podust LM, Garcia JL, Ortiz de Montellano PR Environ Microbiol. 2013 Feb 19. doi: 10.1111/1462-2920.12108. PMID:23489718^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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, Madrona Y, Ortiz de Montellano PR. Cholesterol Ester Oxidation by Mycobacterial Cytochromes P450. J Biol Chem. 2014 Sep 10. pii: jbc.M114.602771. PMID:25210044 doi:http://dx.doi.org/10.1074/jbc.M114.602771
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2yoo"

@@ Line 3: / Line 3: @@
 <StructureSection load='2yoo' size='340' side='right'caption='[[2yoo]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2yoo]] is a 4 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=2YOO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YOO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2yoo]] is a 4 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=2YOO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YOO FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=K2B:(8ALPHA,9BETA)-CHOLEST-4-EN-3-ONE'>K2B</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.69&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bb8|4bb8]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=K2B:(8ALPHA,9BETA)-CHOLEST-4-EN-3-ONE'>K2B</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=2yoo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yoo OCA], [http://pdbe.org/2yoo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2yoo RCSB], [http://www.ebi.ac.uk/pdbsum/2yoo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2yoo ProSAT]</span></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=2yoo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yoo OCA], [https://pdbe.org/2yoo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yoo RCSB], [https://www.ebi.ac.uk/pdbsum/2yoo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yoo ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/CP142_MYCS2 CP142_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 (25R)-26-hydroxycholest-4-en-3-one (alcohol), (25R)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the carboxylic acid (25R)-3-oxocholest-4-en-26-oate. Also able to sequentially oxidize cholesterol itself, not only cholest-4-en-3-one.<ref>PMID:23489718</ref> <ref>PMID:25210044</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Mycs2]]
+[[Category: Mycolicibacterium smegmatis MC2 155]]
-[[Category: Frank, D J]]
+[[Category: Frank DJ]]
-[[Category: Galan, B]]
+[[Category: Galan B]]
-[[Category: Garcia, J L]]
+[[Category: Garcia JL]]
-[[Category: Garcia-Fernandez, E]]
+[[Category: Garcia-Fernandez E]]
-[[Category: Kells, P M]]
+[[Category: Kells PM]]
-[[Category: Montellano, P R.Ortiz de]]
+[[Category: Ortiz de Montellano PR]]
-[[Category: Podust, L M]]
+[[Category: Podust LM]]
-[[Category: Cholesterol metabolism]]
-[[Category: Oxidoreductase]]

2yoo

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Current revision

Cholest-4-en-3-one bound structure of CYP142 from Mycobacterium smegmatis

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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