5g3u

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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5g3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g3u OCA], [http://pdbe.org/5g3u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g3u RCSB], [http://www.ebi.ac.uk/pdbsum/5g3u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g3u ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5g3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g3u OCA], [http://pdbe.org/5g3u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g3u RCSB], [http://www.ebi.ac.uk/pdbsum/5g3u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g3u ProSAT]</span></td></tr>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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<ref>PMID:27466367</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5g3u" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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</StructureSection>
</StructureSection>

Revision as of 08:02, 10 August 2016

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

5g3u, resolution 2.38Å

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