PDBsum entry: 1s16

Isomerase

PDB-id

1s16


	Biological unit* = asymmetric unit, as shown (as deduced by PQS*)

Contents

Description

Header details

Protein chains

Ligands

SO4 ×2

ANP ×2

Metal ions

_MG ×2

Waters ×247

* Residue conservation analysis

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PDB id:

1s16

Name:

Isomerase

Title:

Crystal structure of e. Coli topoisomerase iv pare 43kda subunit complexed with adpnp

Structure:

Topoisomerase iv subunit b. Chain: a, b. Fragment: 43kda subunit. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: pare, nfxd, b3030. Expressed in: escherichia coli. Expression_system_taxid: 562

Biological unit:

Dimer (from PQS)

UniProt:

Chains A, B: P20083 (PARE_ECOLI)

Seq:

Struc:

Seq:

Struc:

Seq:

630 a.a.

Struc:

380 a.a.

Key:		PfamA domain
		Secondary structure			CATH domain

Resolution:

2.10Å

R-factor:

0.224

R-free:

0.240

Authors:

Y.Wei,C.H.Gross

Key ref:

S.Bellon et al. (2004). 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, 48, 1856-1864. [PubMed id: 15105144] [DOI: 10.1128/AAC.48.5.1856-1864.2004]

Date:

05-Jan-04

Release date:

04-May-04

Related entries:

1s14

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Key reference

DOI no: 10.1128/AAC.48.5.1856-1864.2004 Antimicrob Agents Chemother 48:1856-1864 (2004)

PubMed id: 15105144

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.

S.Bellon, J.D.Parsons, Y.Wei, K.Hayakawa, L.L.Swenson, P.S.Charifson, J.A.Lippke, R.Aldape, C.H.Gross.

ABSTRACT

Topoisomerase IV and DNA gyrase are related bacterial type II topoisomerases that utilize the free energy from ATP hydrolysis to catalyze topological changes in the bacterial genome. The essential function of DNA gyrase is the introduction of negative DNA supercoils into the genome, whereas the essential function of topoisomerase IV is to decatenate daughter chromosomes following replication. Here, we report the crystal structures of a 43-kDa N-terminal fragment of Escherichia coli topoisomerase IV ParE subunit complexed with adenylyl-imidodiphosphate at 2.0-A resolution and a 24-kDa N-terminal fragment of the ParE subunit complexed with novobiocin at 2.1-A resolution. The solved ParE structures are strikingly similar to the known gyrase B (GyrB) subunit structures. We also identified single-position equivalent amino acid residues in ParE (M74) and in GyrB (I78) that, when exchanged, increased the potency of novobiocin against topoisomerase IV by nearly 20-fold (to 12 nM). The corresponding exchange in gyrase (I78 M) yielded a 20-fold decrease in the potency of novobiocin (to 1.0 micro M). These data offer an explanation for the observation that novobiocin is significantly less potent against topoisomerase IV than against DNA gyrase. Additionally, the enzyme kinetic parameters were affected. In gyrase, the ATP K(m) increased approximately 5-fold and the V(max) decreased approximately 30%. In contrast, the topoisomerase IV ATP K(m) decreased by a factor of 6, and the V(max) increased approximately 2-fold from the wild-type values. These data demonstrate that the ParE M74 and GyrB I78 side chains impart opposite effects on the enzyme's substrate affinity and catalytic efficiency.

Literature references that cite this PDB file's key reference

PubMed id Reference

19920922 O.Doppelt-Azeroual, F.Moriaud, F.Delfaud, and A.G.de Brevern (2009).
Analysis of HSP90-related folds with MED-SuMo classification approach.

Drug Des Devel Ther, 3, 59-72.

19208647 P.Forterre, and D.Gadelle (2009).
Phylogenomics of DNA topoisomerases: their origin and putative roles in the emergence of modern organisms.

Nucleic Acids Res, 37, 679-692.

18755053 A.J.Schoeffler, and J.M.Berger (2008).
DNA topoisomerases: harnessing and constraining energy to govern chromosome topology.

Q Rev Biophys, 41, 41.

17682095 D.A.Ostrov, J.A.Hernández Prada, P.E.Corsino, K.A.Finton, N.Le, and T.C.Rowe (2007).
Discovery of novel DNA gyrase inhibitors by high-throughput virtual screening.

Antimicrob Agents Chemother, 51, 3688-3698.

17375187 I.Laponogov, D.A.Veselkov, M.K.Sohi, X.S.Pan, A.Achari, C.Yang, J.D.Ferrara, L.M.Fisher, and M.R.Sanderson (2007).
Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target.

PLoS ONE, 2, e301.

PDB code: 2nov

17159922 L.L.Silver (2007).
Multi-targeting by monotherapeutic antibacterials.

Nat Rev Drug Discov, 6, 41-55.

17116675 T.H.Grossman, D.J.Bartels, S.Mullin, C.H.Gross, J.D.Parsons, Y.Liao, A.L.Grillot, D.Stamos, E.R.Olson, P.S.Charifson, and N.Mani (2007).
Dual targeting of GyrB and ParE by a novel aminobenzimidazole class of antibacterial compounds.

Antimicrob Agents Chemother, 51, 657-666.

16569833 N.Mani, C.H.Gross, J.D.Parsons, B.Hanzelka, U.Müh, S.Mullin, Y.Liao, A.L.Grillot, D.Stamos, P.S.Charifson, and T.H.Grossman (2006).
In vitro characterization of the antibacterial spectrum of novel bacterial type II topoisomerase inhibitors of the aminobenzimidazole class.

Antimicrob Agents Chemother, 50, 1228-1237.

16321962 K.Yamashiro, and A.Yamagishi (2005).
Characterization of the DNA gyrase from the thermoacidophilic archaeon Thermoplasma acidophilum.

J Bacteriol, 187, 8531-8536.

15372084 M.B.Schmid (2004).
Seeing is believing: the impact of structural genomics on antimicrobial drug discovery.

Nat Rev Microbiol, 2, 739-746.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.