PDBsum entry 1wbb

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protein dna_rna ligands metals Protein-protein interface(s) links
DNA-binding PDB id
Protein chains
788 a.a. *
Waters ×285
* Residue conservation analysis
PDB id:
Name: DNA-binding
Title: Crystal structure of e. Coli DNA mismatch repair enzyme muts, e38a mutant, in complex with a g.T mismatch
Structure: DNA mismatch repair protein muts. Chain: a, b. Fragment: residues 1-800. Engineered: yes. Mutation: yes. 5'-d( Ap Gp Cp Tp Gp Cp Cp Ap Gp Gp Cp Ap Cp Cp Ap Gp Tp G)-3'. Chain: e. Engineered: yes.
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_variant: plyss. Synthetic: yes. Synthetic: yes
Biol. unit: Tetramer (from PDB file)
2.50Å     R-factor:   0.221     R-free:   0.270
Authors: G.Natrajan,D.Georgijevic,J.H.G.Lebbink,H.H.K.Winterwerp,N.De T.K.Sixma
Key ref:
J.H.Lebbink et al. (2006). Dual role of MutS glutamate 38 in DNA mismatch discrimination and in the authorization of repair. EMBO J, 25, 409-419. PubMed id: 16407973 DOI: 10.1038/sj.emboj.7600936
31-Oct-04     Release date:   18-Jan-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P23909  (MUTS_ECOLI) -  DNA mismatch repair protein MutS
853 a.a.
788 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mismatch repair complex   2 terms 
  Biological process     response to DNA damage stimulus   5 terms 
  Biochemical function     nucleotide binding     11 terms  


DOI no: 10.1038/sj.emboj.7600936 EMBO J 25:409-419 (2006)
PubMed id: 16407973  
Dual role of MutS glutamate 38 in DNA mismatch discrimination and in the authorization of repair.
J.H.Lebbink, D.Georgijevic, G.Natrajan, A.Fish, H.H.Winterwerp, T.K.Sixma, Wind.
MutS plays a critical role in DNA mismatch repair in Escherichia coli by binding to mismatches and initiating repair in an ATP-dependent manner. Mutational analysis of a highly conserved glutamate, Glu38, has revealed its role in mismatch recognition by enabling MutS to discriminate between homoduplex and mismatched DNA. Crystal structures of MutS have shown that Glu38 forms a hydrogen bond to one of the mismatched bases. In this study, we have analyzed the crystal structures, DNA binding and the response to ATP binding of three Glu38 mutants. While confirming the role of the negative charge in initial discrimination, we show that in vivo mismatch repair can proceed even when discrimination is low. We demonstrate that the formation of a hydrogen bond by residue 38 to the mismatched base authorizes repair by inducing intramolecular signaling, which results in the inhibition of rapid hydrolysis of distally bound ATP. This allows formation of the stable MutS-ATP-DNA clamp, a key intermediate in triggering downstream repair events.
  Selected figure(s)  
Figure 1.
Figure 1 Crystal structures of wild-type MutS and E38 variants. (A) Schematic view of the E. coli MutS dimer, with the mismatch-binding monomer A shown in yellow, the supporting monomer B shown in orange and the mismatch containing DNA in blue. (B) Superposition of the mismatch-binding clamp domains and DNA of wild-type and mutant MutS obtained by superposing the C atoms of the mismatch-binding monomer A of all the structures. (C) G.T mismatch binding by the wild-type MutS. (D) G.T mismatch binding by the E38T mutant, with the bound water molecule in red, along with its mF[o]-DF[c] map contoured at 3 (in green). (E) G.T mismatch binding by the E38Q mutant. (F) G.T mismatch binding by E38A, shown with the bound water molecule (in red) along with its mF[o]-DF[c] density map contoured at 3 (in green). Dashed red lines indicate hydrogen bonds and residue 38 in panels C-F is shown in purple. All figures were made using PyMOL (Copyrightę 2004 DeLano Scientific).
Figure 5.
Figure 5 Kinetic response to ATP binding of wild-type MutS and E38 mutants. (A) Magnitude of burst amplitude of ADP formation during the first hydrolytic turnover in a rapid quench ATPase assay in the absence and presence of DNA containing a G.T mismatch. (B) Kinetics of ATP-induced MutS release from mismatched (mm) DNA with a free end and (C) from double end-blocked mismatched DNA determined by SPR.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2006, 25, 409-419) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20167596 J.H.Lebbink, A.Fish, A.Reumer, G.Natrajan, H.H.Winterwerp, and T.K.Sixma (2010).
Magnesium coordination controls the molecular switch function of DNA mismatch repair protein MutS.
  J Biol Chem, 285, 13131-13141.
PDB codes: 2wtu 3k0s
20080735 J.Zhai, and M.M.Hingorani (2010).
Saccharomyces cerevisiae Msh2-Msh6 DNA binding kinetics reveal a mechanism of targeting sites for DNA mismatch repair.
  Proc Natl Acad Sci U S A, 107, 680-685.  
20180598 L.E.Sass, C.Lanyi, K.Weninger, and D.A.Erie (2010).
Single-molecule FRET TACKLE reveals highly dynamic mismatched DNA-MutS complexes.
  Biochemistry, 49, 3174-3190.  
18854319 I.Tessmer, Y.Yang, J.Zhai, C.Du, P.Hsieh, M.M.Hingorani, and D.A.Erie (2008).
Mechanism of MutS searching for DNA mismatches and signaling repair.
  J Biol Chem, 283, 36646-36654.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18406444 P.Hsieh, and K.Yamane (2008).
DNA mismatch repair: molecular mechanism, cancer, and ageing.
  Mech Ageing Dev, 129, 391-407.  
17207499 E.Jacobs-Palmer, and M.M.Hingorani (2007).
The effects of nucleotides on MutS-DNA binding kinetics clarify the role of MutS ATPase activity in mismatch repair.
  J Mol Biol, 366, 1087-1098.  
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
17157869 S.D.Lee, J.A.Surtees, and E.Alani (2007).
Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display distinct requirements for DNA binding domain I in mismatch recognition.
  J Mol Biol, 366, 53-66.  
17141577 S.F.Holmes, K.D.Scarpinato, S.D.McCulloch, R.M.Schaaper, and T.A.Kunkel (2007).
Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif of yeast Msh6.
  DNA Repair (Amst), 6, 293-303.  
16821093 G.Plotz, S.Zeuzem, and J.Raedle (2006).
DNA mismatch repair and Lynch syndrome.
  J Mol Histol, 37, 271-283.  
17012287 L.Manelyte, C.Urbanke, L.Giron-Monzon, and P.Friedhoff (2006).
Structural and functional analysis of the MutS C-terminal tetramerization domain.
  Nucleic Acids Res, 34, 5270-5279.  
16623698 S.H.Jun, T.G.Kim, and C.Ban (2006).
DNA mismatch repair system. Classical and fresh roles.
  FEBS J, 273, 1609-1619.  
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 codes are shown on the right.