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< | ==Structure of Helicobacter pylori type II dehydroquinase in complex with inhibitor compound (2R)-2-(4-methoxybenzyl)-3-dehydroquinic acid== | ||
<StructureSection load='2xb9' size='340' side='right'caption='[[2xb9]], [[Resolution|resolution]] 2.75Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xb9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XB9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XB9 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]] 2.75Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</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=2xb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xb9 OCA], [https://pdbe.org/2xb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xb9 RCSB], [https://www.ebi.ac.uk/pdbsum/2xb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xb9 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AROQ_HELPY AROQ_HELPY] Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xb/2xb9_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2xb9 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The 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<ref>PMID:20815012</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2xb9" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Dehydroquinase 3D structures|Dehydroquinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Helicobacter pylori]] | [[Category: Helicobacter pylori]] | ||
[[Category: Fox | [[Category: Large Structures]] | ||
[[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 13:28, 20 December 2023
Structure of Helicobacter pylori type II dehydroquinase in complex with inhibitor compound (2R)-2-(4-methoxybenzyl)-3-dehydroquinic acidStructure of Helicobacter pylori type II dehydroquinase in complex with inhibitor compound (2R)-2-(4-methoxybenzyl)-3-dehydroquinic acid
Structural highlights
FunctionAROQ_HELPY 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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