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Endonuclease PDB id
1azo
Jmol
Contents
Protein chain
214 a.a. *
Ligands
EDO ×11
Waters ×212
* Residue conservation analysis
PDB id:
1azo
Name: Endonuclease
Title: DNA mismatch repair protein muth from e. Coli
Structure: Muth. Chain: a. Synonym: DNA mismatch repair protein muth. Engineered: yes
Source: Escherichia coli. Organism_taxid: 83333. Strain: k12. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.70Å     R-factor:   0.203     R-free:   0.263
Authors: W.Yang
Key ref:
C.Ban and W.Yang (1998). Structural basis for MutH activation in E.coli mismatch repair and relationship of MutH to restriction endonucleases. EMBO J, 17, 1526-1534. PubMed id: 9482749 DOI: 10.1093/emboj/17.5.1526
Date:
19-Nov-97     Release date:   20-May-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P06722  (MUTH_ECOLI) -  DNA mismatch repair protein mutH
Seq:
Struc: 		229 a.a.
214 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     cytoplasm   1 term 
  Biological process     response to DNA damage stimulus   3 terms 
  Biochemical function     protein binding     5 terms  

 

 
DOI no: 10.1093/emboj/17.5.1526 EMBO J 17:1526-1534 (1998)
PubMed id: 9482749  
 
 
Structural basis for MutH activation in E.coli mismatch repair and relationship of MutH to restriction endonucleases.
C.Ban, W.Yang.
 
  ABSTRACT  
 
MutS, MutL and MutH are the three essential proteins for initiation of methyl-directed DNA mismatch repair to correct mistakes made during DNA replication in Escherichia coli. MutH cleaves a newly synthesized and unmethylated daughter strand 5' to the sequence d(GATC) in a hemi-methylated duplex. Activation of MutH requires the recognition of a DNA mismatch by MutS and MutL. We have crystallized MutH in two space groups and solved the structures at 1.7 and 2.3 A resolution, respectively. The active site of MutH is located at an interface between two subdomains that pivot relative to one another, as revealed by comparison of the crystal structures, and this presumably regulates the nuclease activity. The relative motion of the two subdomains in MutH correlates with the position of a protruding C-terminal helix. This helix appears to act as a molecular lever through which MutS and MutL may communicate the detection of a DNA mismatch and activate MutH. With sequence homology to Sau3AI and structural similarity to PvuII endonuclease, MutH is clearly related to these enzymes by divergent evolution, and this suggests that type II restriction endonucleases evolved from a common ancestor.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 DNA-binding cleft. Orthogonal views of the MutH molecular surface mapped with positive (blue) and negative (red) electrostatic potentials. The molecular surface is generated from the molecule with the most 'open' conformation (the red one in Figure 4A). A bent DNA borrowed from the EcoRV -DNA complex is modeled into the DNA-binding cleft. Loops BC and 67 are partially removed in order to produce an unobstructed view of the cleft. The subdomains, the molecular lever and the conserved residues in the cleft are labeled. 		Figure 4.
Figure 4 Pivoting of the subdomains. (A) A stereo view of the overlay of the three MutH C traces after superimposing the first 60 C atoms at the N-terminus. Every tenth C atom is labeled with a ball. The blue and the red structures are derived from the monoclinic crystal and the yellow one from the orthorhombic crystal. The catalytic residues of the blue molecule, which has the most complete trace, are shown. Three linkers between the two pivoting subdomains are labeled 1, 2 and 3. (B) A simplified diagram of how the molecular lever pivots the C-arm relative to the N-arm. The correlated motion of the lever and the C-arm is denoted by arrows of the same color. Two nearly orthogonal rotations are observed and indicated by blue and green arrows.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1998, 17, 1526-1534) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20961958 M.Laganeckas, M.Margelevicius, and C.Venclovas (2011).
Identification of new homologs of PD-(D/E)XK nucleases by support vector machines trained on data derived from profile-profile alignments.
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20854710 W.Yang (2011).
Nucleases: diversity of structure, function and mechanism.
  Q Rev Biophys, 44, 1.  
  20981145 R.Morita, S.Nakane, A.Shimada, M.Inoue, H.Iino, T.Wakamatsu, K.Fukui, N.Nakagawa, R.Masui, and S.Kuramitsu (2010).
Molecular mechanisms of the whole DNA repair system: a comparison of bacterial and eukaryotic systems.
  J Nucleic Acids, 2010, 179594.  
20375162 S.K.Menon, B.J.Eilers, M.J.Young, and C.M.Lawrence (2010).
The crystal structure of D212 from sulfolobus spindle-shaped virus ragged hills reveals a new member of the PD-(D/E)XK nuclease superfamily.
  J Virol, 84, 5890-5897.
PDB code: 2w8m
19775280 L.S.Li, J.C.Morales, M.Veigl, D.Sedwick, S.Greer, M.Meyers, M.Wagner, R.Fishel, and D.A.Boothman (2009).
DNA mismatch repair (MMR)-dependent 5-fluorouracil cytotoxicity and the potential for new therapeutic targets.
  Br J Pharmacol, 158, 679-692.  
18157157 G.M.Li (2008).
Mechanisms and functions of DNA mismatch repair.
  Cell Res, 18, 85-98.  
18346280 L.M.Iyer, S.Abhiman, and L.Aravind (2008).
MutL homologs in restriction-modification systems and the origin of eukaryotic MORC ATPases.
  Biol Direct, 3, 8.  
17623842 C.R.Guzzo, R.A.Nagem, J.A.Barbosa, and C.S.Farah (2007).
Structure of Xanthomonas axonopodis pv. citri YaeQ reveals a new compact protein fold built around a variation of the PD-(D/E)XK nuclease motif.
  Proteins, 69, 644-651.
PDB code: 2g3w
17559505 E.Dion, L.Li, M.Jean, and F.Belzile (2007).
An Arabidopsis MLH1 mutant exhibits reproductive defects and reveals a dual role for this gene in mitotic recombination.
  Plant J, 51, 431-440.  
17407166 J.Kosinski, E.Kubareva, and J.M.Bujnicki (2007).
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17215294 K.Fukui, H.Kosaka, S.Kuramitsu, and R.Masui (2007).
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17214552 L.Mones, I.Simon, and M.Fuxreiter (2007).
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Restriction endonuclease MvaI is a monomer that recognizes its target sequence asymmetrically.
  Nucleic Acids Res, 35, 2035-2046.
PDB codes: 2oa9 2oaa
17513474 T.Davidsen, H.K.Tuven, M.Bjørås, E.A.Rødland, and T.Tønjum (2007).
Genetic interactions of DNA repair pathways in the pathogen Neisseria meningitidis.
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17135187 G.Plotz, C.Welsch, L.Giron-Monzon, P.Friedhoff, M.Albrecht, A.Piiper, R.M.Biondi, T.Lengauer, S.Zeuzem, and J.Raedle (2006).
Mutations in the MutSalpha interaction interface of MLH1 can abolish DNA mismatch repair.
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16821093 G.Plotz, S.Zeuzem, and J.Raedle (2006).
DNA mismatch repair and Lynch syndrome.
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16619242 N.Danilova (2006).
The evolution of immune mechanisms.
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16772401 R.Ahrends, J.Kosinski, D.Kirsch, L.Manelyte, L.Giron-Monzon, L.Hummerich, O.Schulz, B.Spengler, and P.Friedhoff (2006).
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16623698 S.H.Jun, T.G.Kim, and C.Ban (2006).
DNA mismatch repair system. Classical and fresh roles.
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15659661 E.S.Hong, A.Yeung, P.Funchain, M.M.Slupska, and J.H.Miller (2005).
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16011798 J.Kosinski, M.Feder, and J.M.Bujnicki (2005).
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16209953 J.Y.Lee, J.Chang, N.Joseph, R.Ghirlando, D.N.Rao, and W.Yang (2005).
MutH complexed with hemi- and unmethylated DNAs: coupling base recognition and DNA cleavage.
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PDB codes: 2aoq 2aor
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15720711 M.Feder, and J.M.Bujnicki (2005).
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MLH1 mutations differentially affect meiotic functions in Saccharomyces cerevisiae.
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12560476 G.H.Toedt, R.Krishnan, and P.Friedhoff (2003).
Site-specific protein modification to identify the MutL interface of MutH.
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Single-nucleotide polymorphisms of the Trypanosoma cruzi MSH2 gene support the existence of three phylogenetic lineages presenting differences in mismatch-repair efficiency.
  Genetics, 164, 117-126.  
14527292 M.J.Schofield, and P.Hsieh (2003).
DNA mismatch repair: molecular mechanisms and biological function.
  Annu Rev Microbiol, 57, 579-608.  
14576294 M.Mucke, D.H.Kruger, and M.Reuter (2003).
Diversity of type II restriction endonucleases that require two DNA recognition sites.
  Nucleic Acids Res, 31, 6079-6084.  
12655005 N.K.Raghavendra, and D.N.Rao (2003).
Functional cooperation between exonucleases and endonucleases--basis for the evolution of restriction enzymes.
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12887908 S.Acharya, P.L.Foster, P.Brooks, and R.Fishel (2003).
The coordinated functions of the E. coli MutS and MutL proteins in mismatch repair.
  Mol Cell, 12, 233-246.  
12067333 A.S.Bhagwat, and M.Lieb (2002).
Cooperation and competition in mismatch repair: very short-patch repair and methyl-directed mismatch repair in Escherichia coli.
  Mol Microbiol, 44, 1421-1428.  
12237459 D.J.Rigden, P.Setlow, B.Setlow, I.Bagyan, R.A.Stein, and M.J.Jedrzejas (2002).
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  Protein Sci, 11, 2370-2381.  
12093751 J.M.Hadden, A.C.Déclais, S.E.Phillips, and D.M.Lilley (2002).
Metal ions bound at the active site of the junction-resolving enzyme T7 endonuclease I.
  EMBO J, 21, 3505-3515.
PDB codes: 1m0d 1m0i
12142452 M.Fuxreiter, and I.Simon (2002).
Protein stability indicates divergent evolution of PD-(D/E)XK type II restriction endonucleases.
  Protein Sci, 11, 1978-1983.  
12356742 M.Mücke, G.Grelle, J.Behlke, R.Kraft, D.H.Krüger, and M.Reuter (2002).
EcoRII: a restriction enzyme evolving recombination functions?
  EMBO J, 21, 5262-5268.  
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Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer.
  Genes Chromosomes Cancer, 33, 160-167.  
11742344 N.C.Horton, L.F.Dorner, and J.J.Perona (2002).
Sequence selectivity and degeneracy of a restriction endonuclease mediated by DNA intercalation.
  Nat Struct Biol, 9, 42-47.
PDB code: 1kc6
11934505 P.Friedhoff, B.Sheybani, E.Thomas, C.Merz, and A.Pingoud (2002).
Haemophilus influenzae and Vibrio cholerae genes for mutH are able to fully complement a mutH defect in Escherichia coli.
  FEMS Microbiol Lett, 208, 123-128.  
11809896 T.H.Wu, T.Loh, and M.G.Marinus (2002).
The function of Asp70, Glu77 and Lys79 in the Escherichia coli MutH protein.
  Nucleic Acids Res, 30, 818-822.  
11920679 T.M.Marti, C.Kunz, and O.Fleck (2002).
DNA mismatch repair and mutation avoidance pathways.
  J Cell Physiol, 191, 28-41.  
11557805 A.Pingoud, and A.Jeltsch (2001).
Structure and function of type II restriction endonucleases.
  Nucleic Acids Res, 29, 3705-3727.  
11590160 H.W.Chang, and D.A.Julin (2001).
Structure and function of the Escherichia coli RecE protein, a member of the RecB nuclease domain family.
  J Biol Chem, 276, 46004-46010.  
11557807 I.Kobayashi (2001).
Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution.
  Nucleic Acids Res, 29, 3742-3756.  
11376141 J.T.Drummond, and A.Bellacosa (2001).
Human DNA mismatch repair in vitro operates independently of methylation status at CpG sites.
  Nucleic Acids Res, 29, 2234-2243.  
11557809 S.E.Tsutakawa, and K.Morikawa (2001).
The structural basis of damaged DNA recognition and endonucleolytic cleavage for very short patch repair endonuclease.
  Nucleic Acids Res, 29, 3775-3783.  
11179891 T.K.Sixma (2001).
DNA mismatch repair: MutS structures bound to mismatches.
  Curr Opin Struct Biol, 11, 47-52.  
10911996 A.B.Hickman, Y.Li, S.V.Mathew, E.W.May, N.L.Craig, and F.Dyda (2000).
Unexpected structural diversity in DNA recombination: the restriction endonuclease connection.
  Mol Cell, 5, 1025-1034.
PDB code: 1f1z
10982877 A.Yamamoto, M.J.Schofield, I.Biswas, and P.Hsieh (2000).
Requirement for Phe36 for DNA binding and mismatch repair by Escherichia coli MutS protein.
  Nucleic Acids Res, 28, 3564-3569.  
10944205 D.M.Lilley, and M.F.White (2000).
Resolving the relationships of resolving enzymes.
  Proc Natl Acad Sci U S A, 97, 9351-9353.  
10666447 E.A.Kubareva, H.Thole, A.S.Karyagina, T.S.Oretskaya, A.Pingoud, and V.Pingoud (2000).
Identification of a base-specific contact between the restriction endonuclease SsoII and its recognition sequence by photocross-linking.
  Nucleic Acids Res, 28, 1085-1091.  
10754232 F.S.Gimble (2000).
Invasion of a multitude of genetic niches by mobile endonuclease genes.
  FEMS Microbiol Lett, 185, 99.  
10973051 H.S.Malik, and S.Henikoff (2000).
Dual recognition-incision enzymes might be involved in mismatch repair and meiosis.
  Trends Biochem Sci, 25, 414-418.  
10617645 J.Wang, R.Chen, and D.A.Julin (2000).
A single nuclease active site of the Escherichia coli RecBCD enzyme catalyzes single-stranded DNA degradation in both directions.
  J Biol Chem, 275, 507-513.  
10982859 L.Aravind, K.S.Makarova, and E.V.Koonin (2000).
SURVEY AND SUMMARY: holliday junction resolvases and related nucleases: identification of new families, phyletic distribution and evolutionary trajectories.
  Nucleic Acids Res, 28, 3417-3432.  
10856254 Q.Huai, J.D.Colandene, Y.Chen, F.Luo, Y.Zhao, M.D.Topal, and H.Ke (2000).
Crystal structure of NaeI-an evolutionary bridge between DNA endonuclease and topoisomerase.
  EMBO J, 19, 3110-3118.
PDB code: 1ev7
10886362 S.Hiraga, C.Ichinose, T.Onogi, H.Niki, and M.Yamazoe (2000).
Bidirectional migration of SeqA-bound hemimethylated DNA clusters and pairing of oriC copies in Escherichia coli.
  Genes Cells, 5, 327-341.  
11092821 S.Hiraga (2000).
Dynamic localization of bacterial and plasmid chromosomes.
  Annu Rev Genet, 34, 21-59.  
10690417 A.B.Buermeyer, S.M.Deschênes, S.M.Baker, and R.M.Liskay (1999).
Mammalian DNA mismatch repair.
  Annu Rev Genet, 33, 533-564.  
10199405 C.Ban, M.Junop, and W.Yang (1999).
Transformation of MutL by ATP binding and hydrolysis: a switch in DNA mismatch repair.
  Cell, 97, 85-97.
PDB codes: 1b62 1b63
10601033 D.R.Kim, Y.Dai, C.L.Mundy, W.Yang, and M.A.Oettinger (1999).
Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase.
  Genes Dev, 13, 3070-3080.  
10200960 K.Carlson, L.D.Kosturko, and A.C.Nyström (1999).
Sequence-specific cleavage by bacteriophage T4 endonuclease II in vitro.
  Mol Microbiol, 31, 1395-1405.  
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Type II restriction endonucleases: structural, functional and evolutionary relationships.
  Curr Opin Chem Biol, 3, 578-583.  
10360178 S.E.Tsutakawa, T.Muto, T.Kawate, H.Jingami, N.Kunishima, M.Ariyoshi, D.Kohda, M.Nakagawa, and K.Morikawa (1999).
Crystallographic and functional studies of very short patch repair endonuclease.
  Mol Cell, 3, 621-628.
PDB code: 1vsr
9827806 C.Ban, and W.Yang (1998).
Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis.
  Cell, 95, 541-552.
PDB code: 1bkn
  9811640 D.P.Twomey, L.L.McKay, and D.J.O'Sullivan (1998).
Molecular characterization of the Lactococcus lactis LlaKR2I restriction-modification system and effect of an IS982 element positioned between the restriction and modification genes.
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9653111 R.A.Kovall, and B.W.Matthews (1998).
Structural, functional, and evolutionary relationships between lambda-exonuclease and the type II restriction endonucleases.
  Proc Natl Acad Sci U S A, 95, 7893-7897.  
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.