6hqs

Crystal structure of GcoA F169S bound to syringol

spinqualitylabelsall models 6hqs, resolution 2.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6hqs is a 1 chain structure with sequence from Amycolatopsis sp. ATCC 39116. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.17Å Ligands: 3DM, HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GCOA_AMYS7 Part of a two-component P450 system that efficiently O-demethylates diverse aromatic substrates such as guaiacol and a wide variety of lignin-derived monomers. Is likely involved in lignin degradation, allowing Amycolatopsis sp. ATCC 39116 to catabolize plant biomass. GcoA binds and processes the substrate with electrons supplied by the GcoB subunit. Publication Abstract from PubMed Microbial conversion of aromatic compounds is an emerging and promising strategy for valorization of the plant biopolymer lignin. A critical and often rate-limiting reaction in aromatic catabolism is O-aryl-demethylation of the abundant aromatic methoxy groups in lignin to form diols, which enables subsequent oxidative aromatic ring-opening. Recently, a cytochrome P450 system, GcoAB, was discovered to demethylate guaiacol (2-methoxyphenol), which can be produced from coniferyl alcohol-derived lignin, to form catechol. However, native GcoAB has minimal ability to demethylate syringol (2,6-dimethoxyphenol), the analogous compound that can be produced from sinapyl alcohol-derived lignin. Despite the abundance of sinapyl alcohol-based lignin in plants, no pathway for syringol catabolism has been reported to date. Here we used structure-guided protein engineering to enable microbial syringol utilization with GcoAB. Specifically, a phenylalanine residue (GcoA-F169) interferes with the binding of syringol in the active site, and on mutation to smaller amino acids, efficient syringol O-demethylation is achieved. Crystallography indicates that syringol adopts a productive binding pose in the variant, which molecular dynamics simulations trace to the elimination of steric clash between the highly flexible side chain of GcoA-F169 and the additional methoxy group of syringol. Finally, we demonstrate in vivo syringol turnover in Pseudomonas putida KT2440 with the GcoA-F169A variant. Taken together, our findings highlight the significant potential and plasticity of cytochrome P450 aromatic O-demethylases in the biological conversion of lignin-derived aromatic compounds. Enabling microbial syringol conversion through structure-guided protein engineering.,Machovina MM, Mallinson SJB, Knott BC, Meyers AW, Garcia-Borras M, Bu L, Gado JE, Oliver A, Schmidt GP, Hinchen DJ, Crowley MF, Johnson CW, Neidle EL, Payne CM, Houk KN, Beckham GT, McGeehan JE, DuBois JL Proc Natl Acad Sci U S A. 2019 Jun 24. pii: 1820001116. doi:, 10.1073/pnas.1820001116. PMID:31235604 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

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