View source for 9w56


==Structure of L-glutamate oxidase E617Q mutant in complex with L-glutamate==
<StructureSection load='9w56' size='340' side='right'caption='[[9w56]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9w56]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._X-119-6 Streptomyces sp. X-119-6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9W56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9W56 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9w56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9w56 OCA], [https://pdbe.org/9w56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9w56 RCSB], [https://www.ebi.ac.uk/pdbsum/9w56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9w56 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LGOX_STRSQ LGOX_STRSQ] Catalyzes the oxidative deamination of L-glutamate to 2-ketoglutarate along with the production of ammonia and hydrogen peroxide (PubMed:14769868, PubMed:22197816, Ref.2). Shows strict substrate specificity for L-glutamate, and exhibits only very weak activity with L-aspartate (Ref.2).<ref>PMID:14769868</ref> <ref>PMID:22197816</ref> <ref>PMID:19531050</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
L-Amino acid oxidase (LAAO) is a flavoenzyme that catalyzes the oxidative deamination of L-amino acids, producing alpha-keto acids, ammonia, and hydrogen peroxide. Among LAAOs, L-glutamate oxidase (LGOX) from Streptomyces sp. X-119-6 exhibits exceptionally high substrate specificity for L-glutamate. LGOX is expressed as a homodimeric precursor and undergoes proteolytic processing for maturation. Structural studies revealed that LGOX comprises an FAD-binding domain, a substrate-binding domain, and a helical domain. Conserved residues W653, R124, and Y562 that recognize the alpha-amino and alpha-carboxyl groups of the substrate exist in the putative active site. R305 was identified as a key determinant for side-chain recognition; its substitution with Glu conferred specific activity toward L-arginine, effectively converting LGOX into an L-arginine oxidase. However, the putative substrate binding pocket includes an acidic residue, E617, undesirable for acidic substrates. Therefore, the mechanism of high specificity for L-glutamate remains unclear. To elucidate the molecular basis for the high substrate specificity of LGOX, we determined the structure of LGOX in complex with L-glutamate. Structural and mutational analyses revealed that E617 plays a critical role in substrate binding by aligning the side chain of R305. The loop at the entrance of the tunnel to the substrate-binding site regulates the access of the substrate to the site. Furthermore, E617F and E617K variants acquired L-tyrosine oxidase activity, providing insight into how specificity can be redirected. These findings clarify the substrate recognition mechanism of LGOX and underscore its potential as a robust scaffold for engineering novel amino acid oxidases with tailored specificities.

Substrate recognition mechanisms of L-glutamate oxidase from Streptomyces sp. and its conversion to L-tyrosine oxidase.,Ueda Y, Yano Y, Nakayama N, Takekawa N, Inagaki K, Imada K Protein Sci. 2026 Jan;35(1):e70432. doi: 10.1002/pro.70432. PMID:41432352<ref>PMID:41432352</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9w56" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp. X-119-6]]
[[Category: Imada K]]
[[Category: Inagaki K]]
[[Category: Takekawa N]]
[[Category: Ueda Y]]
[[Category: Yano Y]]