8ws4 | pdb_00008ws4

Crystal structure of the CYP199A4 mutant F182A in complex with 4-methoxybenzoic acid

spinqualitylabelsall models 8ws4, resolution 1.53Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ws4 is a 1 chain structure with sequence from Rhodopseudomonas palustris HaA2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.53Å Ligands: ACT, ANN, HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed P450-catalyzed O-demethylation reactions have recently attracted particular attention because of their potential applications in lignin bioconversion. We recently enabled the peroxygenase activity of CYP199A4, a NADH-dependent cytochrome P450 monooxygenase from Rhodopseudomonas palustris, by engineering a hydrogen peroxide (H(2)O(2)) tunnel. In this report, we reveal by crystallography and molecule dynamics simulations that key residues located at one of the water tunnels in CYP199A4 play a crucial gating role, which enhances the peroxygenase activity by regulating the inflow of H(2)O(2). These results provide a more complete understanding of the mechanism by which monooxygenase is converted into peroxygenase activity through the H(2)O(2) tunnel engineering (HTE) strategy. Furthermore, a library of engineered CYP199A4 peroxygenases was constructed to explore their application potentials for O-demethylation of various methoxy-substituted benzoic acid derivatives. The engineered CYP199A4 peroxygenases showed good functional group tolerance and preferential O-demethylation at the meta- or para-position, indicating potential O-demethylation of H- and G-type lignin monomers. This work reveals the feasibility of the HTE strategy in creating P450 peroxygenase from a mechanistic perspective, laying the foundation for developing an effective P450 O-demethylase applicable in lignin bioconversion. Crucial gating residues govern the enhancement of peroxygenase activity in an engineered cytochrome P450 O-demethylase.,Zhao P, Jiang Y, Wang Q, Chen J, Yao F, Cong Z Chem Sci. 2024 May 3;15(21):8062-8070. doi: 10.1039/d4sc02418d. eCollection 2024 , May 29. PMID:38817576 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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