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2xco

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Revision as of 10:49, 13 April 2022

The 3.1A crystal structure of the catalytic core (B'A' region) of Staphylococcus aureus DNA Gyrase

Structural highlights

2xco is a 1 chain structure with sequence from Staan. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2xcs, 2xct, 2xcr, 2xcq
Activity:	DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GYRB_STAAN] 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 (By similarity).

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

Despite the success of genomics in identifying new essential bacterial genes, there is a lack of sustainable leads in antibacterial drug discovery to address increasing multidrug resistance. Type IIA topoisomerases cleave and religate DNA to regulate DNA topology and are a major class of antibacterial and anticancer drug targets, yet there is no well developed structural basis for understanding drug action. Here we report the 2.1 A crystal structure of a potent, new class, broad-spectrum antibacterial agent in complex with Staphylococcus aureus DNA gyrase and DNA, showing a new mode of inhibition that circumvents fluoroquinolone resistance in this clinically important drug target. The inhibitor 'bridges' the DNA and a transient non-catalytic pocket on the two-fold axis at the GyrA dimer interface, and is close to the active sites and fluoroquinolone binding sites. In the inhibitor complex the active site seems poised to cleave the DNA, with a single metal ion observed between the TOPRIM (topoisomerase/primase) domain and the scissile phosphate. This work provides new insights into the mechanism of topoisomerase action and a platform for structure-based drug design of a new class of antibacterial agents against a clinically proven, but conformationally flexible, enzyme class.

Type IIA topoisomerase inhibition by a new class of antibacterial agents.,Bax BD, Chan PF, Eggleston DS, Fosberry A, Gentry DR, Gorrec F, Giordano I, Hann MM, Hennessy A, Hibbs M, Huang J, Jones E, Jones J, Brown KK, Lewis CJ, May EW, Saunders MR, Singh O, Spitzfaden CE, Shen C, Shillings A, Theobald AJ, Wohlkonig A, Pearson ND, Gwynn MN Nature. 2010 Aug 19;466(7309):935-40. Epub 2010 Aug 4. PMID:20686482^[1]

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

References

↑ Bax BD, Chan PF, Eggleston DS, Fosberry A, Gentry DR, Gorrec F, Giordano I, Hann MM, Hennessy A, Hibbs M, Huang J, Jones E, Jones J, Brown KK, Lewis CJ, May EW, Saunders MR, Singh O, Spitzfaden CE, Shen C, Shillings A, Theobald AJ, Wohlkonig A, Pearson ND, Gwynn MN. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature. 2010 Aug 19;466(7309):935-40. Epub 2010 Aug 4. PMID:20686482 doi:10.1038/nature09197

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/2xco"

@@ Line 3: / Line 3: @@
 <StructureSection load='2xco' size='340' side='right'caption='[[2xco]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xco]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Staan Staan]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XCO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XCO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xco]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staan Staan]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XCO FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xcs|2xcs]], [[2xct|2xct]], [[2xcr|2xcr]], [[2xcq|2xcq]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2xcs|2xcs]], [[2xct|2xct]], [[2xcr|2xcr]], [[2xcq|2xcq]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [https://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://proteopedia.org/fgij/fg.htm?mol=2xco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xco OCA], [http://pdbe.org/2xco PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xco RCSB], [http://www.ebi.ac.uk/pdbsum/2xco PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xco ProSAT]</span></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=2xco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xco OCA], [https://pdbe.org/2xco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xco RCSB], [https://www.ebi.ac.uk/pdbsum/2xco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xco ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GYRB_STAAN GYRB_STAAN]] 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 (By similarity).
+[[https://www.uniprot.org/uniprot/GYRB_STAAN GYRB_STAAN]] 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 (By similarity).
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

2xco

From Proteopedia

Revision as of 10:49, 13 April 2022

The 3.1A crystal structure of the catalytic core (B'A' region) of Staphylococcus aureus DNA Gyrase

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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