4kpe: Difference between revisions

Revision as of 09:05, 7 December 2022

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 Streptococcus pneumoniae TIGR4 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	AF5, MG
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]

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^[3]

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, 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:https://dx.doi.org/10.1098/rsob.160157

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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:https://dx.doi.org/10.1098/rsob.160157

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <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>
+<table><tr><td colspan='2'>[[4kpe]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_TIGR4 Streptococcus pneumoniae TIGR4] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. 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 [https://proteopedia.org/fgij/fg.htm?mol=4KPE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AF5:(7AR,8R)-8-AMINO-4-CYCLOPROPYL-12-FLUORO-1-OXO-4,7,7A,8,9,10-HEXAHYDRO-1H-PYRROLO[1,2 1,7]AZEPINO[2,3-H]QUINOLINE-2-CARBOXYLIC+ACID'>AF5</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AF5:(7AR,8R)-8-AMINO-4-CYCLOPROPYL-12-FLUORO-1-OXO-4,7,7A,8,9,10-HEXAHYDRO-1H-PYRROLO[1,2 1,7]AZEPINO[2,3-H]QUINOLINE-2-CARBOXYLIC+ACID'>AF5</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">[[3foe|3foe]], [[3fof|3fof]], [[2nov|2nov]], [[3k9f|3k9f]], [[3ksa|3ksa]], [[3ksb|3ksb]], [[3ltn|3ltn]], [[3rad|3rad]], [[3rae|3rae]], [[3raf|3raf]], [[4koe|4koe]], [[4kpf|4kpf]]</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=4kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kpe OCA], [https://pdbe.org/4kpe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kpe RCSB], [https://www.ebi.ac.uk/pdbsum/4kpe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kpe ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">parC, SP_0855 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=170187 STRPN]), parE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=170187 STRPN])</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=4kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kpe OCA], [http://pdbe.org/4kpe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kpe RCSB], [http://www.ebi.ac.uk/pdbsum/4kpe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kpe ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PARC_STRPN 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.<ref>PMID:17375187</ref> <ref>PMID:20596531</ref>  [[http://www.uniprot.org/uniprot/PARE_STRPN 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.<ref>PMID:17375187</ref> <ref>PMID:20596531</ref>
+[https://www.uniprot.org/uniprot/PARC_STRPN 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.<ref>PMID:17375187</ref> <ref>PMID:20596531</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 20: @@
 ==See Also==
-*[[Topoisomerase|Topoisomerase]]
+*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
 == References ==
 <references/>
@@ Line 29: / Line 26: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Strpn]]
+[[Category: Streptococcus pneumoniae TIGR4]]
-[[Category: Cirz, R T]]
+[[Category: Synthetic construct]]
-[[Category: Fisher, L M]]
+[[Category: Cirz RT]]
-[[Category: Laponogov, I]]
+[[Category: Fisher LM]]
-[[Category: Moser, H E]]
+[[Category: Laponogov I]]
-[[Category: Pan, X S]]
+[[Category: Moser HE]]
-[[Category: Sanderson, M R]]
+[[Category: Pan X-S]]
-[[Category: Vesekov, D A]]
+[[Category: Sanderson MR]]
-[[Category: Wagman, A S]]
+[[Category: Vesekov DA]]
-[[Category: Achn-245]]
+[[Category: Wagman AS]]
-[[Category: Isomerase-dna-inhibitor complex]]
-[[Category: Protein-dna cleavage complex]]
-[[Category: Quinolone]]
-[[Category: Topoisomerase iia]]

4kpe: Difference between revisions

Revision as of 09:05, 7 December 2022

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

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