5g3u

The structure of the L-tryptophan oxidase VioA from Chromobacterium violaceum in complex with its inhibitor 2-(1H-indol-3-ylmethyl)prop-2- enoic acid

spinqualitylabelsall models 5g3u, resolution 2.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5g3u is a 2 chain structure with sequence from Chromobacterium violaceum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.377Å Ligands: CSS, FDA, GOL, ITW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VIOA_CHRVO Publication Abstract from PubMed Violacein is a natural purple pigment of Chromobacterium violaceum with potential medical applications as antimicrobial, antiviral and anticancer drugs. The initial step of violacein biosynthesis is the oxidative conversion of L-tryptophan into the corresponding alpha-imine catalyzed by the flavoenzyme L-tryptophan oxidase (VioA). A substrate-related (3-(1H-indol-3-yl)-2-methylpropanoic acid, IAA) and a product-related (2-(1H-indol-3-ylmethyl)prop-2-enoic acid, IEA) competitive VioA inhibitor was synthesized for subsequent kinetic and X-ray crystallographic investigations. Structures of the binary VioA/FADH2 and of the ternary VioA/FADH2/IEA complex were resolved. VioA forms a `loosely associated` homodimer as indicated by small-angle X-ray scattering experiments. VioA belongs to the GR2 family of FAD-dependent oxidoreductases according to the structurally conserved cofactor binding domain. The substrate-binding domain of VioA is mainly responsible for the specific recognition of L-tryptophan. Other canonical amino acids were efficiently discriminated with a minor conversion of L-phenylalanine. Furthermore, 7-aza-tryptophan, 1-methyl-tryptophan, 5-methyl-tryptophan and 5-fluoro-tryptophan were efficient substrates of VioA. The ternary product-related VioA structure indicated involvement of protein domain movement during enzyme catalysis. Extensive structure-based mutagenesis in combination with enzyme kinetics (using L-tryptophan and substrate analogs) identified Arg64, Lys269 and Tyr309 as key catalytic residues of VioA. An increased enzyme activity of protein variant H163A in the presence of L-phenylalanine indicated a functional role of the residues in substrate-binding. The combined structural and mutational analyses lead to the detailed understanding of VioA substrate recognition. Related strategies for the in vivo synthesis of novel violacein derivatives are discussed. Biosynthesis of Violacein: Structure and Function of L-Tryptophan Oxidase VioA from Chromobacterium violaceum.,Fuller JJ, Ropke R, Krausze J, Rennhack KE, Daniel NP, Blankenfeldt W, Schulz S, Jahn D, Moser J J Biol Chem. 2016 Jul 27. pii: jbc.M116.741561. PMID:27466367 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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