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PDBsum entry 1mx0

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protein ligands metals Protein-protein interface(s) links
Isomerase PDB id
1mx0
Jmol
Contents
Protein chains
(+ 0 more) 461 a.a. *
Ligands
ANP ×6
Metals
_MG ×6
_NA
Waters ×811
* Residue conservation analysis
PDB id:
1mx0
Name: Isomerase
Title: Structure of topoisomerase subunit
Structure: Type ii DNA topoisomerase vi subunit b. Chain: a, b, c, d, e, f. Engineered: yes
Source: Sulfolobus shibatae. Organism_taxid: 2286. Gene: top6b. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.30Å     R-factor:   0.219     R-free:   0.263
Authors: K.D.Corbett,J.M.Berger
Key ref:
K.D.Corbett and J.M.Berger (2003). Structure of the topoisomerase VI-B subunit: implications for type II topoisomerase mechanism and evolution. EMBO J, 22, 151-163. PubMed id: 12505993 DOI: 10.1093/emboj/cdg008
Date:
01-Oct-02     Release date:   07-Jan-03    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
O05207  (TOP6B_SULSH) -  Type 2 DNA topoisomerase 6 subunit B
Seq:
Struc:
 
Seq:
Struc:
530 a.a.
461 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.5.99.1.3  - Dna topoisomerase (ATP-hydrolyzing).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP-dependent breakage, passage and rejoining of double-stranded DNA.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     chromosome   1 term 
  Biological process     DNA topological change   1 term 
  Biochemical function     nucleic acid binding     4 terms  

 

 
DOI no: 10.1093/emboj/cdg008 EMBO J 22:151-163 (2003)
PubMed id: 12505993  
 
 
Structure of the topoisomerase VI-B subunit: implications for type II topoisomerase mechanism and evolution.
K.D.Corbett, J.M.Berger.
 
  ABSTRACT  
 
Type IIA and type IIB topoisomerases each possess the ability to pass one DNA duplex through another in an ATP-dependent manner. The role of ATP in the strand passage reaction is poorly understood, particularly for the type IIB (topoisomerase VI) family. We have solved the structure of the ATP-binding subunit of topoisomerase VI (topoVI-B) in two states: an unliganded monomer and a nucleotide-bound dimer. We find that topoVI-B is highly structurally homologous to the entire 40-43 kDa ATPase region of type IIA topoisomerases and MutL proteins. Nucleotide binding to topoVI-B leads to dimerization of the protein and causes dramatic conformational changes within each protomer. Our data demonstrate that type IIA and type IIB topoisomerases have descended from a common ancestor and reveal how ATP turnover generates structural signals in the reactions of both type II topoisomerase families. When combined with the structure of the A subunit to create a picture of the intact topoisomerase VI holoenzyme, the ATP-driven motions of topoVI-B reveal a simple mechanism for strand passage by the type IIB topoisomerases.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 TopoVI-B' monomer. (A) Domain organization of type II topoisomerases. Key functional modules of type IIA and IIB topoisomerases are labeled as follows: GHKL (yellow), CAP (green) and toprim (red). A conserved 'transducer' domain (Trans.) is shown in orange and the H2TH domain of topoVI-B' is shown in pink. The split of the A and B regions in prokaryotic type IIA enzymes into discrete subunits is indicated by the double hash mark. The active-site tyrosines (yellow circles) are labeled as 'Y' and conserved acidic residues within the toprim fold are shown as blue circles. While the GHKL and toprim folds of type IIB topoisomerases are identifiable by sequence homology, the type IIB CAP region (striped green) has no sequence homology to the equivalent fold in type IIA proteins. Furthermore, the N- to C-terminal orientation of the CAP and toprim modules is swapped between the two type II topoisomerase families. (B) Structure-based sequence alignment of topoVI-B' with the ATPase regions of E.coli GyrB and MutL. The secondary structural elements of topoVI-B' are shown below the sequences. The three domains are colored as in (A). Residue numbering is that of topoVI-B' followed by that of GyrB in parentheses. Highlighted in blue are the GHKL motifs identified by Bergerat et al. (1997). Highlighted in red is the invariant lysine (427 in topoVI-B', 337 in GyrB) that contacts the -phosphate of bound nucleotide and highlighted in green is a highly conserved asparagine (375 in topoVI-B', 271 in GyrB) that serves as an anchoring element between the GHKL and transducer domains. (C) Structure of the monomer (apo) form of topoVI-B'. Domains are colored as in (A). Secondary structural elements are labeled as in (B). (B) was generated by ALSCRIPT (Barton, 1993) and (C) with RIBBONS (Carson, 1991).
Figure 3.
Figure 3 Comparison of topoVI-B', GyrB and MutL dimer structures. (A) Structure of the AMP-PNP bound topoVI-B' dimer. Coloring is as in Figure 1C. Two views are shown: front (top) and top-down (bottom). Bound nucleotides and Mg2+ ions are shown in blue. (B) and (C) AMP-PNP-bound dimer structures of GyrB (Wigley et al., 1991) and MutL (Ban et al., 1999), respectively. The GHKL and transducer domains are colored as in (A), and the views are equivalent for all three proteins.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2003, 22, 151-163) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22108601 S.M.Vos, E.M.Tretter, B.H.Schmidt, and J.M.Berger (2011).
All tangled up: how cells direct, manage and exploit topoisomerase function.
  Nat Rev Mol Cell Biol, 12, 827-841.  
20675723 A.J.Schoeffler, A.P.May, and J.M.Berger (2010).
A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function.
  Nucleic Acids Res, 38, 7830-7844.
PDB code: 3nuh
19059997 J.Roca (2009).
Topoisomerase II: a fitted mechanism for the chromatin landscape.
  Nucleic Acids Res, 37, 721-730.  
19361515 R.M.Immormino, L.E.Metzger, P.N.Reardon, D.E.Dollins, B.S.Blagg, and D.T.Gewirth (2009).
Different poses for ligand and chaperone in inhibitor-bound Hsp90 and GRP94: implications for paralog-specific drug design.
  J Mol Biol, 388, 1033-1042.
PDB codes: 2exl 2fxs 2gfd
18755053 A.J.Schoeffler, and J.M.Berger (2008).
DNA topoisomerases: harnessing and constraining energy to govern chromosome topology.
  Q Rev Biophys, 41, 41.  
18206974 E.J.Sacho, F.A.Kadyrov, P.Modrich, T.A.Kunkel, and D.A.Erie (2008).
Direct visualization of asymmetric adenine-nucleotide-induced conformational changes in MutL alpha.
  Mol Cell, 29, 112-121.  
18403371 F.Mueller-Planitz, and D.Herschlag (2008).
Coupling between ATP binding and DNA cleavage by DNA topoisomerase II: A unifying kinetic and structural mechanism.
  J Biol Chem, 283, 17463-17476.  
18647240 N.D.Thomsen, and J.M.Berger (2008).
Structural frameworks for considering microbial protein- and nucleic acid-dependent motor ATPases.
  Mol Microbiol, 69, 1071-1090.  
17603498 K.D.Corbett, P.Benedetti, and J.M.Berger (2007).
Holoenzyme assembly and ATP-mediated conformational dynamics of topoisomerase VI.
  Nat Struct Mol Biol, 14, 611-619.
PDB code: 2q2e
17355868 L.Costenaro, J.G.Grossmann, C.Ebel, and A.Maxwell (2007).
Modular structure of the full-length DNA gyrase B subunit revealed by small-angle X-ray scattering.
  Structure, 15, 329-339.  
16920739 K.D.Corbett, and J.M.Berger (2006).
Structural basis for topoisomerase VI inhibition by the anti-Hsp90 drug radicicol.
  Nucleic Acids Res, 34, 4269-4277.
PDB code: 2hkj
17116242 M.Jain, A.K.Tyagi, and J.P.Khurana (2006).
Overexpression of putative topoisomerase 6 genes from rice confers stress tolerance in transgenic Arabidopsis plants.
  FEBS J, 273, 5245-5260.  
15849317 D.Gadelle, C.Bocs, M.Graille, and P.Forterre (2005).
Inhibition of archaeal growth and DNA topoisomerase VI activities by the Hsp90 inhibitor radicicol.
  Nucleic Acids Res, 33, 2310-2317.  
16100112 H.Wei, A.J.Ruthenburg, S.K.Bechis, and G.L.Verdine (2005).
Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase.
  J Biol Chem, 280, 37041-37047.
PDB codes: 1zxm 1zxn
15647268 J.Vaughn, S.Huang, I.Wessel, T.K.Sorensen, T.Hsieh, L.H.Jensen, P.B.Jensen, M.Sehested, and J.L.Nitiss (2005).
Stability of the topoisomerase II closed clamp conformation may influence DNA-stimulated ATP hydrolysis.
  J Biol Chem, 280, 11920-11929.  
15939019 K.D.Corbett, and J.M.Berger (2005).
Structural dissection of ATP turnover in the prototypical GHL ATPase TopoVI.
  Structure, 13, 873-882.
PDB codes: 1z59 1z5a 1z5b 1z5c
15139806 K.D.Corbett, and J.M.Berger (2004).
Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases.
  Annu Rev Biophys Biomol Struct, 33, 95.  
14583603 V.H.Oestergaard, L.Bjergbaek, C.Skouboe, L.Giangiacomo, B.R.Knudsen, and A.H.Andersen (2004).
The transducer domain is important for clamp operation in human DNA topoisomerase IIalpha.
  J Biol Chem, 279, 1684-1691.  
15123700 V.H.Oestergaard, L.Giangiacomo, L.Bjergbaek, B.R.Knudsen, and A.H.Andersen (2004).
Hindering the strand passage reaction of human topoisomerase IIalpha without disturbing DNA cleavage, ATP hydrolysis, or the operation of the N-terminal clamp.
  J Biol Chem, 279, 28093-28099.  
12618182 K.D.Corbett, and J.M.Berger (2003).
Emerging roles for plant topoisomerase VI.
  Chem Biol, 10, 107-111.  
12963818 S.Classen, S.Olland, and J.M.Berger (2003).
Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187.
  Proc Natl Acad Sci U S A, 100, 10629-10634.
PDB codes: 1pvg 1q1d 1qzr
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.