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4kpe

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Revision as of 15:53, 29 January 2020

Novel fluoroquinolones in complex with topoisomerase IV from S. pneumoniae and E-site G-gate

Structural highlights

4kpe is a 8 chain structure with sequence from Strpn. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3foe, 3fof, 2nov, 3k9f, 3ksa, 3ksb, 3ltn, 3rad, 3rae, 3raf, 4koe, 4kpf
Gene:	parC, SP_0855 (STRPN), parE (STRPN)
Activity:	DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PARC_STRPN] Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.^[1] ^[2] [PARE_STRPN] Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.^[3] ^[4]

Publication Abstract from PubMed

As part of a programme of synthesizing and investigating the biological properties of new fluoroquinolone antibacterials and their targeting of topoisomerase IV from Streptococcus pneumoniae, we have solved the X-ray structure of the complexes of two new 7,8-bridged fluoroquinolones (with restricted C7 group rotation favouring tight binding) in complex with the topoisomerase IV from S. pneumoniae and an 18-base-pair DNA binding site-the E-site-found by our DNA mapping studies to bind drug strongly in the presence of topoisomerase IV (Leo et al. 2005 J. Biol. Chem. 280, 14 252-14 263, doi:10.1074/jbc.M500156200). Although the degree of antibiotic resistance towards fluoroquinolones is much lower than that of beta-lactams and a range of ribosome-bound antibiotics, there is a pressing need to increase the diversity of members of this successful clinically used class of drugs. The quinolone moiety of the new 7,8-bridged agents ACHN-245 and ACHN-454 binds similarly to that of clinafloxocin, levofloxacin, moxifloxacin and trovofloxacin but the cyclic scaffold offers the possibility of chemical modification to produce interactions with other topoisomerase residues at the active site.

Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones.,Laponogov I, Pan XS, Veselkov DA, Cirz RT, Wagman A, Moser HE, Fisher LM, Sanderson MR Open Biol. 2016 Sep;6(9). pii: rsob.160157. doi: 10.1098/rsob.160157. PMID:27655731^[5]

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

References

↑ Laponogov I, Veselkov DA, Sohi MK, Pan XS, Achari A, Yang C, Ferrara JD, Fisher LM, Sanderson MR. Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target. PLoS ONE. 2007 Mar 21;2(3):e301. PMID:17375187 doi:10.1371/journal.pone.0000301
↑ Laponogov I, Pan XS, Veselkov DA, McAuley KE, Fisher LM, Sanderson MR. Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS One. 2010 Jun 28;5(6):e11338. PMID:20596531 doi:10.1371/journal.pone.0011338
↑ Laponogov I, Veselkov DA, Sohi MK, Pan XS, Achari A, Yang C, Ferrara JD, Fisher LM, Sanderson MR. Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target. PLoS ONE. 2007 Mar 21;2(3):e301. PMID:17375187 doi:10.1371/journal.pone.0000301
↑ Laponogov I, Pan XS, Veselkov DA, McAuley KE, Fisher LM, Sanderson MR. Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS One. 2010 Jun 28;5(6):e11338. PMID:20596531 doi:10.1371/journal.pone.0011338
↑ Laponogov I, Pan XS, Veselkov DA, Cirz RT, Wagman A, Moser HE, Fisher LM, Sanderson MR. Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones. Open Biol. 2016 Sep;6(9). pii: rsob.160157. doi: 10.1098/rsob.160157. PMID:27655731 doi:http://dx.doi.org/10.1098/rsob.160157

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/4kpe"

@@ Line 1: / Line 1: @@
 ==Novel fluoroquinolones in complex with topoisomerase IV from S. pneumoniae and E-site G-gate==
-<StructureSection load='4kpe' size='340' side='right' caption='[[4kpe]], [[Resolution|resolution]] 3.43&Aring;' scene=''>
+<StructureSection load='4kpe' size='340' side='right'caption='[[4kpe]], [[Resolution|resolution]] 3.43&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4kpe]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Strpn Strpn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KPE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KPE FirstGlance]. <br>
@@ Line 28: / Line 28: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Strpn]]
 [[Category: Cirz, R T]]

4kpe

From Proteopedia

Revision as of 15:53, 29 January 2020

Novel fluoroquinolones in complex with topoisomerase IV from S. pneumoniae and E-site G-gate

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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