4hz0

From Proteopedia

(Difference between revisions)

Revision as of 15:57, 4 August 2016

Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.

Structural highlights

4hz0 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:	4hz5, 4hyp, 4hym, 4hy1, 4hxz, 4ggl, 4gfn, 4gee, 4hxw
Gene:	b3030, DNA topoisomerase IV subunit B ParE, JW2998, nfxD, parE (ECOLI)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PARE_ECOLI] Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule. MukB stimulates the relaxation activity of topoisomerase IV and also has a modest effect on decatenation.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication. The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. A pyrrolopyrimidine scaffold was identified from a pharmacophore-based fragment screen with optimization potential. Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity.

Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.,Tari LW, Trzoss M, Bensen DC, Li X, Chen Z, Lam T, Zhang J, Creighton CJ, Cunningham ML, Kwan B, Stidham M, Shaw KJ, Lightstone FC, Wong SE, Nguyen TB, Nix J, Finn J Bioorg Med Chem Lett. 2012 Dec 5. pii: S0960-894X(12)01475-8. doi:, 10.1016/j.bmcl.2012.11.032. PMID:23352267^[4]

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

References

↑ Pitts SL, Liou GF, Mitchenall LA, Burgin AB, Maxwell A, Neuman KC, Osheroff N. Use of divalent metal ions in the DNA cleavage reaction of topoisomerase IV. Nucleic Acids Res. 2011 Jun;39(11):4808-17. doi: 10.1093/nar/gkr018. Epub 2011, Feb 7. PMID:21300644 doi:http://dx.doi.org/10.1093/nar/gkr018
↑ Bellon S, Parsons JD, Wei Y, Hayakawa K, Swenson LL, Charifson PS, Lippke JA, Aldape R, Gross CH. Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24 and 43 kilodaltons): a single residue dictates differences in novobiocin potency against topoisomerase IV and DNA gyrase. Antimicrob Agents Chemother. 2004 May;48(5):1856-64. PMID:15105144
↑ Li Y, Stewart NK, Berger AJ, Vos S, Schoeffler AJ, Berger JM, Chait BT, Oakley MG. Escherichia coli condensin MukB stimulates topoisomerase IV activity by a direct physical interaction. Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18832-7. doi:, 10.1073/pnas.1008678107. Epub 2010 Oct 4. PMID:20921377 doi:http://dx.doi.org/10.1073/pnas.1008678107
↑ Tari LW, Trzoss M, Bensen DC, Li X, Chen Z, Lam T, Zhang J, Creighton CJ, Cunningham ML, Kwan B, Stidham M, Shaw KJ, Lightstone FC, Wong SE, Nguyen TB, Nix J, Finn J. Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity. Bioorg Med Chem Lett. 2012 Dec 5. pii: S0960-894X(12)01475-8. doi:, 10.1016/j.bmcl.2012.11.032. PMID:23352267 doi:http://dx.doi.org/10.1016/j.bmcl.2012.11.032

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/4hz0"

@@ Line 1: / Line 1: @@
 ==Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.==
 <StructureSection load='4hz0' size='340' side='right' caption='[[4hz0]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4hz0]] is a 2 chain structure with sequence from [http://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=4HZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HZ0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4hz0]] 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=4HZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HZ0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1AV:7-(1H-IMIDAZOL-1-YL)-2-(PYRIDIN-3-YL)[1,3]THIAZOLO[5,4-D]PYRIMIDIN-5-AMINE'>1AV</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hz5|4hz5]], [[4hyp|4hyp]], [[4hym|4hym]], [[4hy1|4hy1]], [[4hxz|4hxz]], [[4ggl|4ggl]], [[4gfn|4gfn]], [[4gee|4gee]], [[4hxw|4hxw]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b3030, DNA topoisomerase IV subunit B ParE, JW2998, nfxD, parE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 Escherichia coli K-12])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b3030, DNA topoisomerase IV subunit B ParE, JW2998, nfxD, parE ([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=4hz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hz0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hz0 RCSB], [http://www.ebi.ac.uk/pdbsum/4hz0 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=4hz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hz0 OCA], [http://pdbe.org/4hz0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hz0 RCSB], [http://www.ebi.ac.uk/pdbsum/4hz0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hz0 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4hz0" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Escherichia coli k-12]]
+[[Category: Ecoli]]
 [[Category: Bensen, D C]]
 [[Category: Tari, L W]]

4hz0

From Proteopedia

Revision as of 15:57, 4 August 2016

Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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