9ji6 | pdb_00009ji6

CYP105A1 R84A complexed with diclofenac (DIF)

spinqualitylabelsall models 9ji6, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ji6 is a 1 chain structure with sequence from Streptomyces griseolus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: DIF, EDO, HEM, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CPXE_STRGO Publication Abstract from PubMed Streptomyces griseolus CYP105A1 exhibits monooxygenase activity to a wide variety of structurally different substrates with regio- and stereospecificity, making its application range broad. Our previous studies have shown that CYP105A1 wild type and its variants metabolize 12 types of nonsteroidal anti-inflammatory drugs (NSAIDs). In particular, the R84A variant exhibited a high activity against many NSAIDs. We successfully crystallized complexes of wild-type CYP105A1 (WT) and the R84A variant with diclofenac (DIF) or flufenamic acid (FLF). In the WT, the carboxyl group of DIF formed a charged hydrogen bond with Arg84. In contrast, in R84A, the carboxyl group formed two bidentate charged hydrogen bonds with Arg73. The C4' atom of the benzene ring of DIF, which undergoes hydroxylation by WT and R84A, was positioned approximately 4 A from the heme iron. Binding of FLF was nearly the same in both WT and R84A. The carboxyl group of FLF formed charged hydrogen bonds with Arg73. In both WT and R84A, FLF appeared to be fixed by this charged hydrogen bonding with Arg73 during the reaction, and the C4' atom, which undergoes hydroxylation, must face the heme iron. Thus, the dihedral angles of the two N-C bonds connecting the two benzene rings of FLF needed to rotate by 78 degrees and -71 degrees , respectively. The temperature factors of the F-G loop, helix F, and helix G of R84A were remarkably higher than those of WT. This suggests that these regions in R84A are much more flexible compared to those of WT, which may consequently affect substrate binding and product release. Structure-Function Analysis of Streptomyces griseolus CYP105A1 in the Metabolism of Nonsteroidal Anti-inflammatory Drugs.,Takita T, Wada M, Yamagata M, Kamata S, Mizutani K, Yogo Y, Hamada M, Yasuda K, Mikami B, Sakaki T, Yasukawa K Biochemistry. 2025 Jan 21;64(2):468-478. doi: 10.1021/acs.biochem.4c00652. Epub , 2025 Jan 3. PMID:39752145 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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