PDBsum entry 2aoq

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protein dna_rna metals links
Hydrolase/DNA PDB id
Protein chain
220 a.a. *
_CA ×2
Waters ×154
* Residue conservation analysis
PDB id:
Name: Hydrolase/DNA
Title: Crystal structure of muth-unmethylated DNA complex
Structure: 5'-d( Gp Cp Ap Tp Gp Ap Tp Cp Ap Tp Gp C)-3'. Chain: b, c. Engineered: yes. DNA mismatch repair protein muth. Chain: a. Synonym: methyl-directed mismatch repair protein. Engineered: yes
Source: Synthetic: yes. Haemophilus influenzae. Organism_taxid: 727. Gene: muth. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.20Å     R-factor:   0.199     R-free:   0.220
Authors: J.Y.Lee,J.Chang,N.Joseph,R.Ghirlando,D.N.Rao,W.Yang
Key ref:
J.Y.Lee et al. (2005). MutH complexed with hemi- and unmethylated DNAs: coupling base recognition and DNA cleavage. Mol Cell, 20, 155-166. PubMed id: 16209953 DOI: 10.1016/j.molcel.2005.08.019
13-Aug-05     Release date:   11-Oct-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P44688  (MUTH_HAEIN) -  DNA mismatch repair protein MutH
223 a.a.
220 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     nucleic acid phosphodiester bond hydrolysis   5 terms 
  Biochemical function     hydrolase activity     4 terms  


DOI no: 10.1016/j.molcel.2005.08.019 Mol Cell 20:155-166 (2005)
PubMed id: 16209953  
MutH complexed with hemi- and unmethylated DNAs: coupling base recognition and DNA cleavage.
J.Y.Lee, J.Chang, N.Joseph, R.Ghirlando, D.N.Rao, W.Yang.
MutH initiates mismatch repair by nicking the transiently unmethylated daughter strand 5' to a GATC sequence. Here, we report crystal structures of MutH complexed with hemimethylated and unmethylated GATC substrates. Both structures contain two Ca2+ ions jointly coordinated by a conserved aspartate and the scissile phosphate, as observed in the restriction endonucleases BamHI and BglI. In the hemimethylated complexes, the active site is more compact and DNA cleavage is more efficient. The Lys residue in the conserved DEK motif coordinates the nucleophilic water in conjunction with the phosphate 3' to the scissile bond; the same Lys is also hydrogen bonded with a carbonyl oxygen in the DNA binding module. We propose that this Lys, which is conserved in many restriction endonucleases and is replaced by Glu or Gln in BamHI and BglII, is a sensor for DNA binding and the linchpin that couples base recognition and DNA cleavage.
  Selected figure(s)  
Figure 1.
Figure 1. Ribbon Diagrams of the MutH-DNA Complexes
Figure 3.
Figure 3. The DNAs and DNA-MutH Interactions
  The above figures are reprinted by permission from Cell Press: Mol Cell (2005, 20, 155-166) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20854710 W.Yang (2011).
Nucleases: diversity of structure, function and mechanism.
  Q Rev Biophys, 44, 1.  
20200253 A.Goulet, M.Pina, P.Redder, D.Prangishvili, L.Vera, J.Lichière, N.Leulliot, H.van Tilbeurgh, M.Ortiz-Lombardia, V.Campanacci, and C.Cambillau (2010).
ORF157 from the archaeal virus Acidianus filamentous virus 1 defines a new class of nuclease.
  J Virol, 84, 5025-5031.
PDB codes: 3ii2 3ii3 3ild 3ile
21060849 S.Namadurai, D.Jain, D.S.Kulkarni, C.R.Tabib, P.Friedhoff, D.N.Rao, and D.T.Nair (2010).
The C-terminal domain of the MutL homolog from Neisseria gonorrhoeae forms an inverted homodimer.
  PLoS One, 5, e13726.
PDB code: 3ncv
19789272 F.J.Olorunniji, and W.M.Stark (2009).
The catalytic residues of Tn3 resolvase.
  Nucleic Acids Res, 37, 7590-7602.  
19446525 J.Zhang, X.Xing, A.B.Herr, and C.E.Bell (2009).
Crystal structure of E. coli RecE protein reveals a toroidal tetramer for processing double-stranded DNA breaks.
  Structure, 17, 690-702.
PDB code: 3h4r
19304745 Y.S.Chung, T.Brendler, S.Austin, and A.Guarné (2009).
Structural insights into the cooperative binding of SeqA to a tandem GATC repeat.
  Nucleic Acids Res, 37, 3143-3152.
PDB code: 3fmt
18157157 G.M.Li (2008).
Mechanisms and functions of DNA mismatch repair.
  Cell Res, 18, 85-98.  
18310077 K.Fukui, M.Nishida, N.Nakagawa, R.Masui, and S.Kuramitsu (2008).
Bound nucleotide controls the endonuclease activity of mismatch repair enzyme MutL.
  J Biol Chem, 283, 12136-12145.  
18953336 W.Yang (2008).
An equivalent metal ion in one- and two-metal-ion catalysis.
  Nat Struct Mol Biol, 15, 1228-1231.  
17407166 J.Kosinski, E.Kubareva, and J.M.Bujnicki (2007).
A model of restriction endonuclease MvaI in complex with DNA: a template for interpretation of experimental data and a guide for specificity engineering.
  Proteins, 68, 324-336.  
17214552 L.Mones, I.Simon, and M.Fuxreiter (2007).
Metal-binding sites at the active site of restriction endonuclease BamHI can conform to a one-ion mechanism.
  Biol Chem, 388, 73-78.  
17142111 W.Yang (2007).
Human MutLalpha: the jack of all trades in MMR is also an endonuclease.
  DNA Repair (Amst), 6, 135-139.  
16524590 J.R.Horton, K.Liebert, M.Bekes, A.Jeltsch, and X.Cheng (2006).
Structure and substrate recognition of the Escherichia coli DNA adenine methyltransferase.
  J Mol Biol, 358, 559-570.
PDB code: 2g1p
16473850 J.R.Horton, X.Zhang, R.Maunus, Z.Yang, G.G.Wilson, R.J.Roberts, and X.Cheng (2006).
DNA nicking by HinP1I endonuclease: bending, base flipping and minor groove expansion.
  Nucleic Acids Res, 34, 939-948.
PDB codes: 2fkc 2fkh 2fl3 2flc
16601679 M.Nowotny, and W.Yang (2006).
Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release.
  EMBO J, 25, 1924-1933.
PDB codes: 2g8f 2g8h 2g8i 2g8k 2g8u 2g8v 2g8w
16772401 R.Ahrends, J.Kosinski, D.Kirsch, L.Manelyte, L.Giron-Monzon, L.Hummerich, O.Schulz, B.Spengler, and P.Friedhoff (2006).
Identifying an interaction site between MutH and the C-terminal domain of MutL by crosslinking, affinity purification, chemical coding and mass spectrometry.
  Nucleic Acids Res, 34, 3169-3180.  
16600865 W.Yang, J.Y.Lee, and M.Nowotny (2006).
Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity.
  Mol Cell, 22, 5.  
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.