3p99

Sterol 14alpha-demethylase (CYP51) from Trypanosoma brucei in complex with delta7-14alpha-methylene-cyclopropyl-dihydrolanosterolSterol 14alpha-demethylase (CYP51) from Trypanosoma brucei in complex with delta7-14alpha-methylene-cyclopropyl-dihydrolanosterol

Structural highlights 3p99 is a 4 chain structure with sequence from Trypanosoma brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q385E8_TRYB2 Publication Abstract from PubMed Sterol 14alpha-demethylase (CYP51) that catalyzes the removal of the 14alpha-methyl group from the sterol nucleus is an essential enzyme in sterol biosynthesis, a primary target for clinical and agricultural antifungal azoles and an emerging target for antitrypanosomal chemotherapy. Here, we present the crystal structure of Trypanosoma (T) brucei CYP51 in complex with the substrate analog 14alpha-methylenecyclopropyl-Delta7-24,25-dihydrolanosterol (MCP). This sterol binds tightly to all protozoan CYP51s and acts as a competitive inhibitor of F105-containing (plant-like) T. brucei and Leishmania (L) infantum orthologs, but it has a much stronger, mechanism-based inhibitory effect on I105-containing (animal/fungi-like) T. cruzi CYP51. Depicting substrate orientation in the conserved CYP51 binding cavity, the complex specifies the roles of the contact amino acid residues and sheds new light on CYP51 substrate specificity. It also provides an explanation for the effect of MCP on T. cruzi CYP51. Comparison with the ligand-free and azole-bound structures supports the notion of structural rigidity as the characteristic feature of the CYP51 substrate binding cavity, confirming the enzyme as an excellent candidate for structure-directed design of new drugs, including mechanism-based substrate analog inhibitors. Structural complex of sterol 14alpha-demethylase (CYP51) with 14alpha-methylenecyclopropyl-Delta7-24, 25-dihydrolanosterol.,Hargrove TY, Wawrzak Z, Liu J, Waterman MR, Nes WD, Lepesheva GI J Lipid Res. 2012 Feb;53(2):311-20. Epub 2011 Nov 30. PMID:22135275 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

spinqualitylabelsall models 3p99, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image