View source for 9blv


==Proteus vulgaris tryptophan indole-lyase complexed with L-Trp and benzimidazole==
<StructureSection load='9blv' size='340' side='right'caption='[[9blv]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9blv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Proteus_vulgaris Proteus vulgaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BLV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BLV 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]] 1.78&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JO:2-{[(E)-{3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYLIDENE]AMINO}PROP-2-ENOIC+ACID'>0JO</scene>, <scene name='pdbligand=A1A2Z:N-({3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]pyridin-4-yl}methyl)-L-tryptophan'>A1A2Z</scene>, <scene name='pdbligand=BZI:BENZIMIDAZOLE'>BZI</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PLT:[3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHYL]-L-TRYPTOPHANE'>PLT</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=9blv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9blv OCA], [https://pdbe.org/9blv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9blv RCSB], [https://www.ebi.ac.uk/pdbsum/9blv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9blv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TNAA_PROVU TNAA_PROVU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tryptophan indole lyase (TIL; [E.C. 4.1.99.1]) is a bacterial pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes reversible beta-elimination of indole from L-tryptophan. The mechanism of elimination of indole from L-tryptophan starts with the formation of an external aldimine of the substrate and PLP, followed by deprotonation of the alpha-CH of the substrate, forming a resonance-stabilized quinonoid intermediate. Proton transfer to C3 of the indole ring and carbon-carbon bond cleavage of the quinonoid intermediate provide indole and aminoacrylate bound to PLP, which then releases indole, followed by iminopyruvate. We have now determined the X-ray crystal structures of TIL complexes with (3S)-dioxindolyl-l-alanine, an inhibitor, and with substrates L-tryptophan, 7-aza-L-tryptophan, and S-ethyl-l-cysteine (SEC) in the presence of benzimidazole (BZI), an isostere of the product indole. These structures show a mixture of gem-diamine, external aldimine, quinonoid, and aminoacrylate intermediates, in both open and closed active site conformations. In the closed conformations of L-tryptophan, (3S)-dioxindolyl-l-alanine, and 7-aza-L-tryptophan complexes, hydrogen bonds form between Asp-133 with N1 of the ligand heterocyclic ring and NE2 of His-458 in the small domain of TIL. This hydrogen bond also forms in the BZI complex with the aminoacrylate intermediates formed from both L-tryptophan and SEC. The closed quinonoid complex of 7-aza-L-tryptophan shows that the azaindole ring in the closed conformation is bent out of plane of the Cbeta-C3 bond by about 40 degrees , putting it in a geometry that leads toward the transition-state geometry. Thus, both conformational dynamics and substrate activation play critical roles in the reaction mechanism of the TIL.

Structural Snapshots of Proteus vulgaris Tryptophan Indole-Lyase Reveal Insights into the Catalytic Mechanism.,Phillips RS, Brown SM, Patel RS ACS Catal. 2024 Jul 18;14(15):11498-11511. doi: 10.1021/acscatal.4c03232. , eCollection 2024 Aug 2. PMID:39114092<ref>PMID:39114092</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9blv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Proteus vulgaris]]
[[Category: Phillips RS]]