3dp0: Difference between revisions
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< | ==Crystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) from Helicobacter pylori in complex with compound 3m== | ||
<StructureSection load='3dp0' size='340' side='right'caption='[[3dp0]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3dp0]] is a 6 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=3DP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DP0 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]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2BC:N-[(1E)-(3,5-DIBROMO-2,4-DIHYDROXYPHENYL)METHYLIDENE]NAPHTHALENE-2-CARBOHYDRAZIDE'>2BC</scene>, <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=3dp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dp0 OCA], [https://pdbe.org/3dp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dp0 RCSB], [https://www.ebi.ac.uk/pdbsum/3dp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dp0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q5G940_HELPX Q5G940_HELPX] Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs.[HAMAP-Rule:MF_00406] Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs (By similarity).[SAAS:SAAS00205551] | |||
== 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/dp/3dp0_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=3dp0 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The discovery of HpFabZ inhibitors is now of special interest in the treatment of various gastric diseases. In this work, three series of derivatives (compounds 3, 4, and 5) were designed, synthesized, and their biological activities were investigated as potential HpFabZ inhibitors in a two phased manner. First, we designed and synthesized two series of derivatives (3a-r and 4a-u) and evaluated the enzyme-based assay against HpFabZ. Five compounds (3i-k, 3m, and 3q) showed potential inhibitory activity, with IC(50) values less than 2 muM. Second, a focused combinatorial library containing 280 molecules was designed employing the LD1.0 program. Twelve compounds (5a-l) were selected and synthesized. The activity of the most potent compound 5h (IC(50) = 0.86 muM) was 46 times higher than that of the hit 1. The high hit rate and the potency of the new HpFabZ inhibitors demonstrated the efficiency of the strategy for the focused library design and virtual screening. | |||
Discovering potent inhibitors against the beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) of Helicobacter pylori: structure-based design, synthesis, bioassay, and crystal structure determination.,He L, Zhang L, Liu X, Li X, Zheng M, Li H, Yu K, Chen K, Shen X, Jiang H, Liu H J Med Chem. 2009 Apr 23;52(8):2465-81. PMID:19309082<ref>PMID:19309082</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3dp0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures|Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Helicobacter pylori]] | [[Category: Helicobacter pylori]] | ||
[[Category: He | [[Category: Large Structures]] | ||
[[Category: Jiang | [[Category: He L]] | ||
[[Category: Liu | [[Category: Jiang H]] | ||
[[Category: Liu | [[Category: Liu H]] | ||
[[Category: Shen | [[Category: Liu X]] | ||
[[Category: Zhang | [[Category: Shen X]] | ||
[[Category: Zhang L]] | |||
Latest revision as of 18:13, 1 November 2023
Crystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) from Helicobacter pylori in complex with compound 3mCrystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) from Helicobacter pylori in complex with compound 3m
Structural highlights
FunctionQ5G940_HELPX Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs.[HAMAP-Rule:MF_00406] Involved in unsaturated fatty acids biosynthesis. Catalyzes the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs (By similarity).[SAAS:SAAS00205551] 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 discovery of HpFabZ inhibitors is now of special interest in the treatment of various gastric diseases. In this work, three series of derivatives (compounds 3, 4, and 5) were designed, synthesized, and their biological activities were investigated as potential HpFabZ inhibitors in a two phased manner. First, we designed and synthesized two series of derivatives (3a-r and 4a-u) and evaluated the enzyme-based assay against HpFabZ. Five compounds (3i-k, 3m, and 3q) showed potential inhibitory activity, with IC(50) values less than 2 muM. Second, a focused combinatorial library containing 280 molecules was designed employing the LD1.0 program. Twelve compounds (5a-l) were selected and synthesized. The activity of the most potent compound 5h (IC(50) = 0.86 muM) was 46 times higher than that of the hit 1. The high hit rate and the potency of the new HpFabZ inhibitors demonstrated the efficiency of the strategy for the focused library design and virtual screening. Discovering potent inhibitors against the beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) of Helicobacter pylori: structure-based design, synthesis, bioassay, and crystal structure determination.,He L, Zhang L, Liu X, Li X, Zheng M, Li H, Yu K, Chen K, Shen X, Jiang H, Liu H J Med Chem. 2009 Apr 23;52(8):2465-81. PMID:19309082[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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