3jzf: Difference between revisions
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New page: '''Unreleased structure''' The entry 3jzf is ON HOLD Authors: Orth, P. Description: CRYSTAL STRUCTURE OF BIOTIN CARBOXYLASE FROM E. COLI IN COMPLEX WITH BENZIMIDAZOLES SERIES ''Page s... |
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The | ==Crystal structure of biotin carboxylase from E. Coli in complex with benzimidazoles series== | ||
<StructureSection load='3jzf' size='340' side='right'caption='[[3jzf]], [[Resolution|resolution]] 2.13Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3jzf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JZF 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]] 2.13Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=JZK:2-[(2-CHLOROBENZYL)AMINO]-1-(CYCLOHEXYLMETHYL)-1H-BENZIMIDAZOLE-5-CARBOXAMIDE'>JZK</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=3jzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jzf OCA], [https://pdbe.org/3jzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jzf RCSB], [https://www.ebi.ac.uk/pdbsum/3jzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jzf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ACCC_ECOLI ACCC_ECOLI] This protein is a component of the acetyl coenzyme A carboxylase complex; first, biotin carboxylase catalyzes the carboxylation of the carrier protein and then the transcarboxylase transfers the carboxyl group to form malonyl-CoA. | |||
== 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/jz/3jzf_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=3jzf ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The biotin carboxylase (AccC) is part of the multi-component bacterial acetyl coenzyme-A carboxylase (ACCase) and is essential for pathogen survival. We describe herein the affinity optimization of an initial hit to give 2-(2-chlorobenzylamino)-1-(cyclohexylmethyl)-1H-benzo[d]imidazole-5-carbox amide (1), which was identified using our proprietary Automated Ligand Identification System (ALIS).(1) The X-ray co-crystal structure of 1 was solved and revealed several key interactions and opportunities for further optimization in the ATP site of AccC. Structure Based Drug Design (SBDD) and parallel synthetic approaches resulted in a novel series of AccC inhibitors, exemplified by (R)-2-(2-chlorobenzylamino)-1-(2,3-dihydro-1H-inden-1-yl)-1H-imidazo[4,5-b ]pyridine-5-carboxamide (40). This compound is a potent and selective inhibitor of bacterial AccC with an IC(50) of 20 nM and a MIC of 0.8 microg/mL against a sensitized strain of Escherichia coli (HS294 E. coli). | |||
Discovery and optimization of antibacterial AccC inhibitors.,Cheng CC, Shipps GW Jr, Yang Z, Sun B, Kawahata N, Soucy KA, Soriano A, Orth P, Xiao L, Mann P, Black T Bioorg Med Chem Lett. 2009 Dec 1;19(23):6507-14. Epub 2009 Oct 28. PMID:19875284<ref>PMID:19875284</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3jzf" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Acetyl-CoA carboxylase 3D structures|Acetyl-CoA carboxylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli K-12]] | |||
[[Category: Large Structures]] | |||
[[Category: Orth P]] | |||
Latest revision as of 08:06, 6 September 2023
Crystal structure of biotin carboxylase from E. Coli in complex with benzimidazoles series
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