2xc3

X-ray structure of Mycobacterium tuberculosis cyp125 bound to the reverse type I inhibitor

spinqualitylabelsall models 2xc3, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xc3 is a 1 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: HEM, RT8 Related: 2x5w, 2x5l Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CP125_MYCTU] Catalyzes the C-27 hydroxylation of cholest-4-en-3-one and cholesterol and subsequently oxidizes the alcohol of the former to the cholest-4-en-3-one-27-oic acid via the aldehyde intermediate. Not required to incorporate the cholesterol side-chain carbon atoms into cellular lipids. Publication Abstract from PubMed Cytochrome P450 CYP125A1 of Mycobacteriumtuberculosis, a potential therapeutic target for tuberculosis in humans, initiates degradation of the aliphatic chain of host cholesterol and is essential for establishing M. tuberculosis infection in a mouse model of disease. We explored the interactions of CYP125A1 with a reverse type I inhibitor by X-ray structure analysis and UV-vis spectroscopy. Compound LP10 (alpha-[(4-methylcyclohexyl)carbonyl amino]-N-4-pyridinyl-1H-indole-3-propanamide), previously identified as a potent type II inhibitor of Trypanosomacruzi CYP51, shifts CYP125A1 to a water-coordinated low-spin state upon binding with low micromolar affinity. When LP10 is present in the active site, the crystal structure and spectral characteristics both demonstrate changes in lipophilic and electronic properties favoring coordination of the iron axial water ligand. These results provide an insight into the structural requirements for developing selective CYP125A1 inhibitors. Reverse type I inhibitor of Mycobacteriumtuberculosis CYP125A1.,Ouellet H, Kells PM, Ortiz de Montellano PR, Podust LM Bioorg Med Chem Lett. 2011 Jan 1;21(1):332-7. Epub 2010 Nov 5. PMID:21109436 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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