6to2 | pdb_00006to2

Crystal structure of CYP154C5 from Nocardia farcinica in complex with 5alpha-Androstan-3-one

spinqualitylabelsall models 6to2, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6to2 is a 2 chain structure with sequence from Nocardia farcinica IFM 10152. 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, HEM, NQ8 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5YNS8_NOCFA Publication Abstract from PubMed CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16a-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16alpha-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternate binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that water entrance to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15alpha-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5a-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure-function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation. CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering.,Bracco P, Wijma HJ, Nicolai B, Rodriguez Buitrago JA, Klunemann T, Vila A, Schrepfer P, Blankenfeldt W, Janssen DB, Schallmey A Chembiochem. 2020 Nov 4. doi: 10.1002/cbic.202000735. PMID:33145893 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

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