3jzi

From Proteopedia

(Difference between revisions)

Revision as of 05:02, 7 February 2016

Crystal structure of biotin carboxylase from E. Coli in complex with benzimidazole series

Structural highlights

3jzi is a 2 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3jzf
Gene:	accC, fabG, b3256, JW3224 (ECOLI)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cheng CC, Shipps GW Jr, Yang Z, Sun B, Kawahata N, Soucy KA, Soriano A, Orth P, Xiao L, Mann P, Black T. Discovery and optimization of antibacterial AccC inhibitors. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6507-14. Epub 2009 Oct 28. PMID:19875284 doi:10.1016/j.bmcl.2009.10.057

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3jzi"

@@ Line 2: / Line 2: @@
 <StructureSection load='3jzi' size='340' side='right' caption='[[3jzi]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3jzi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JZI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JZI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3jzi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JZI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JZI FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JZL:7-AMINO-2-[(2-CHLOROBENZYL)AMINO]-1-{[(1S,2S)-2-HYDROXYCYCLOHEPTYL]METHYL}-1H-BENZIMIDAZOLE-5-CARBOXAMIDE'>JZL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jzf|3jzf]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">accC, fabG, b3256, JW3224 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">accC, fabG, b3256, JW3224 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3jzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jzi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3jzi RCSB], [http://www.ebi.ac.uk/pdbsum/3jzi PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3jzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jzi OCA], [http://pdbe.org/3jzi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jzi RCSB], [http://www.ebi.ac.uk/pdbsum/3jzi PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=3jzi ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3jzi" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Biotin carboxylase|Biotin carboxylase]]
+*[[Acetyl-CoA carboxylase|Acetyl-CoA carboxylase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Escherichia coli]]
+[[Category: Ecoli]]
 [[Category: Black, T]]
 [[Category: Cheng, C]]

3jzi

From Proteopedia

Revision as of 05:02, 7 February 2016

Crystal structure of biotin carboxylase from E. Coli in complex with benzimidazole series

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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