4duh

From Proteopedia

(Difference between revisions)

Revision as of 20:50, 4 August 2016

Crystal structure of 24 kDa domain of E. coli DNA gyrase B in complex with small molecule inhibitor

Structural highlights

4duh 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:	1kzn, 1aj6
Gene:	gyrB, acrB, himB, hisU, nalC, parA, pcbA, b3699, JW5625 (ECOLI)
Activity:	DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GYRB_ECOLI] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Bacterial DNA gyrase is a well-established and validated target for the development of novel antibacterials. Starting from the available structural information about the binding of the natural product inhibitor, clorobiocin, we identified a novel series of 4'-methyl-N(2)-phenyl-[4,5'-bithiazole]-2,2'-diamine inhibitors of gyrase B with a low micromolar inhibitory activity by implementing a two-step structure-based design procedure. This novel class of DNA gyrase inhibitors was extensively investigated by various techniques (differential scanning fluorimetry, surface plasmon resonance, and microscale thermophoresis). The binding mode of the potent inhibitor 18 was revealed by X-ray crystallography, confirming our initial in silico binding model. Furthermore, the high resolution of the complex structure allowed for the placement of the Gly97-Ser108 flexible loop, thus revealing its role in binding of this class of compounds. The crystal structure of the complex protein G24 and inhibitor 18 provides valuable information for further optimization of this novel class of DNA gyrase B inhibitors.

Structure-based discovery of substituted 4,5'-bithiazoles as novel DNA gyrase inhibitors.,Brvar M, Perdih A, Renko M, Anderluh G, Turk D, Solmajer T J Med Chem. 2012 Jul 26;55(14):6413-26. Epub 2012 Jul 5. PMID:22731783^[4]

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

References

↑ Noble CG, Maxwell A. The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two metal-ion mechanism. J Mol Biol. 2002 Apr 26;318(2):361-71. PMID:12051843 doi:http://dx.doi.org/10.1016/S0022-2836(02)00049-9
↑ Sissi C, Chemello A, Vazquez E, Mitchenall LA, Maxwell A, Palumbo M. DNA gyrase requires DNA for effective two-site coordination of divalent metal ions: further insight into the mechanism of enzyme action. Biochemistry. 2008 Aug 19;47(33):8538-45. doi: 10.1021/bi800480j. Epub 2008 Jul, 22. PMID:18642932 doi:http://dx.doi.org/10.1021/bi800480j
↑ Schoeffler AJ, May AP, Berger JM. A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function. Nucleic Acids Res. 2010 Jul 31. PMID:20675723 doi:10.1093/nar/gkq665
↑ Brvar M, Perdih A, Renko M, Anderluh G, Turk D, Solmajer T. Structure-based discovery of substituted 4,5'-bithiazoles as novel DNA gyrase inhibitors. J Med Chem. 2012 Jul 26;55(14):6413-26. Epub 2012 Jul 5. PMID:22731783 doi:10.1021/jm300395d

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4duh"

@@ Line 1: / Line 1: @@
 ==Crystal structure of 24 kDa domain of E. coli DNA gyrase B in complex with small molecule inhibitor==
 <StructureSection load='4duh' size='340' side='right' caption='[[4duh]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4duh]] 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=4DUH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DUH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4duh]] 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=4DUH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DUH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RLI:4-{[4-METHYL-2-(PROPANOYLAMINO)-4,5-BI-1,3-THIAZOL-2-YL]AMINO}BENZOIC+ACID'>RLI</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1kzn|1kzn]], [[1aj6|1aj6]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gyrB, acrB, himB, hisU, nalC, parA, pcbA, b3699, JW5625 ([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">gyrB, acrB, himB, hisU, nalC, parA, pcbA, b3699, JW5625 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] </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=4duh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4duh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4duh RCSB], [http://www.ebi.ac.uk/pdbsum/4duh 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=4duh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4duh OCA], [http://pdbe.org/4duh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4duh RCSB], [http://www.ebi.ac.uk/pdbsum/4duh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4duh ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4duh" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Escherichia coli]]
+[[Category: Ecoli]]
 [[Category: Brvar, M]]
 [[Category: Perdih, A]]

4duh

From Proteopedia

Revision as of 20:50, 4 August 2016

Crystal structure of 24 kDa domain of E. coli DNA gyrase B in complex with small molecule inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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