2xb8: Difference between revisions
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<StructureSection load='2xb8' size='340' side='right'caption='[[2xb8]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='2xb8' size='340' side='right'caption='[[2xb8]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xb8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2xb8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XB8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XB8 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=XNW:(1R,2R,4S,5R)-1,4,5-TRIHYDROXY-2-(4-METHOXYBENZYL)-3-OXOCYCLOHEXANECARBOXYLIC+ACID'>XNW</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=XNW:(1R,2R,4S,5R)-1,4,5-TRIHYDROXY-2-(4-METHOXYBENZYL)-3-OXOCYCLOHEXANECARBOXYLIC+ACID'>XNW</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=2xb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xb8 OCA], [https://pdbe.org/2xb8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xb8 RCSB], [https://www.ebi.ac.uk/pdbsum/2xb8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xb8 ProSAT]</span></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=2xb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xb8 OCA], [https://pdbe.org/2xb8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xb8 RCSB], [https://www.ebi.ac.uk/pdbsum/2xb8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xb8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/AROQ_MYCTU AROQ_MYCTU] Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Fox | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Gonzalez-Bello | [[Category: Fox GC]] | ||
[[Category: Llamas-Saiz | [[Category: Gonzalez-Bello C]] | ||
[[Category: Otero | [[Category: Llamas-Saiz AL]] | ||
[[Category: Otero JM]] | |||
[[Category: Tizon | [[Category: Tizon L]] | ||
[[Category: | [[Category: Van Raaij MJ]] | ||
Latest revision as of 13:27, 20 December 2023
Structure of Mycobacterium tuberculosis type II dehydroquinase in complex with inhibitor compound (2R)-2-(4-methoxybenzyl)-3- dehydroquinic acidStructure of Mycobacterium tuberculosis type II dehydroquinase in complex with inhibitor compound (2R)-2-(4-methoxybenzyl)-3- dehydroquinic acid
Structural highlights
FunctionAROQ_MYCTU Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe binding mode of several substrate analogues, (2R)-2-benzyl-3-dehydroquinic acids 4, which are potent reversible competitive inhibitors of type II dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway, has been investigated by structural and computational studies. The crystal structures of Mycobacterium tuberculosis and Helicobacter pylori DHQ2 in complex with one of the most potent inhibitor, p-methoxybenzyl derivative 4 a, have been solved at 2.40 A and 2.75 A, respectively. This has allowed the resolution of the M. tuberculosis DHQ2 loop containing residues 20-25 for the first time. These structures show the key interactions of the aromatic ring in the active site of both enzymes and additionally reveal an important change in the conformation and flexibility of the loop that closes over substrate binding. The loop conformation and the binding mode of compounds 4 b-d has been also studied by molecular dynamics simulations, which suggest that the benzyl group of inhibitors 4 prevent appropriate orientation of the catalytic tyrosine of the loop for proton abstraction and disrupts its basicity. Understanding the Key Factors that Control the Inhibition of Type II Dehydroquinase by (2R)-2-Benzyl-3-dehydroquinic Acids.,Peon A, Otero JM, Tizon L, Prazeres VF, Llamas-Saiz AL, Fox GC, van Raaij MJ, Lamb H, Hawkins AR, Gago F, Castedo L, Gonzalez-Bello C ChemMedChem. 2010 Sep 2. PMID:20815012[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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