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4uro

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Revision as of 17:02, 5 August 2016

Crystal Structure of Staph GyraseB 24kDa in complex with Novobiocin

Structural highlights

4uro is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4url, 4urm, 4urn
Activity:	DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GYRB_STAAU] 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.[HAMAP-Rule:MF_01898]

Publication Abstract from PubMed

Bacterial resistance to antibiotics continues to pose serious challenges as the discovery rate for new antibiotics fades. Kibdelomycin is one of the rare, novel, natural product antibiotics discovered recently that inhibits the bacterial DNA synthesis enzymes gyrase and topoisomerase IV. It is a broad-spectrum, Gram-positive antibiotic without cross-resistance to known gyrase inhibitors, including clinically effective quinolones. To understand its mechanism of action, binding mode, and lack of cross-resistance, we have co-crystallized kibdelomycin and novobiocin with the N-terminal domains of Staphylococcus aureus gyrase B (24 kDa) and topo IV (ParE, 24 and 43 kDa). Kibdelomycin shows a unique "dual-arm", U-shaped binding mode in both crystal structures. The pyrrolamide moiety in the lower part of kibdelomycin penetrates deeply into the ATP-binding site pocket, whereas the isopropyl-tetramic acid and sugar moiety of the upper part thoroughly engage in polar interactions with a surface patch of the protein. The isoproramic acid (1,3-dioxopyrrolidine) and a tetrahydropyran acetate group (Sugar A) make polar contact with a surface area consisting of helix alpha4 and the flexible loop connecting helices alpha3 and alpha4. The two arms are connected together by a rigid decalin linker that makes van del Waals contacts with the protein backbone. This "dual-arm", U-shaped, multicontact binding mode of kibdelomycin is unique and distinctively different from binding modes of other known gyrase inhibitors (e.g., coumarins and quinolones), which explains its lack of cross-resistance and low frequency of resistance. The crystal structures reported in this paper should enable design and discovery of analogues with better properties and antibacterial spectrum.

Structures of Kibdelomycin Bound to Staphylococcus aureus GyrB and ParE Showed a Novel U-Shaped Binding Mode.,Lu J, Patel S, Sharma N, Soisson SM, Kishii R, Takei M, Fukuda Y, Lumb KJ, Singh SB ACS Chem Biol. 2014 Jul 3. PMID:24992706^[1]

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

References

↑ Lu J, Patel S, Sharma N, Soisson SM, Kishii R, Takei M, Fukuda Y, Lumb KJ, Singh SB. Structures of Kibdelomycin Bound to Staphylococcus aureus GyrB and ParE Showed a Novel U-Shaped Binding Mode. ACS Chem Biol. 2014 Jul 3. PMID:24992706 doi:http://dx.doi.org/10.1021/cb5001197

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/4uro"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Staph GyraseB 24kDa in complex with Novobiocin==
 <StructureSection load='4uro' size='340' side='right' caption='[[4uro]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4url|4url]], [[4urm|4urm]], [[4urn|4urn]]</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=4uro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uro OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uro RCSB], [http://www.ebi.ac.uk/pdbsum/4uro 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=4uro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uro OCA], [http://pdbe.org/4uro PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uro RCSB], [http://www.ebi.ac.uk/pdbsum/4uro PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uro 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 4uro" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Gyrase|Gyrase]]
 == References ==
 <references/>

4uro

From Proteopedia

Revision as of 17:02, 5 August 2016

Crystal Structure of Staph GyraseB 24kDa in complex with Novobiocin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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