4apy | pdb_00004apy

Ethylene glycol-bound form of P450 CYP125A3 from Mycobacterium smegmatis

spinqualitylabelsall models 4apy, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4apy is a 1 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 2Å Ligands: CL, EDO, HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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