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PDBsum entry 1eyf

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protein metals links
DNA binding protein PDB id
1eyf
Jmol
Contents
Protein chain
92 a.a. *
Metals
_ZN
* Residue conservation analysis
PDB id:
1eyf
Name: DNA binding protein
Title: Refined structure of the DNA methyl phosphotriester repair domain of e. Coli ada
Structure: Ada regulatory protein. Chain: a. Fragment: n-terminal 10 kda domain. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 25 models
Authors: Y.Lin,V.Dotsch,T.Wintner,K.Peariso,L.C.Myers,J.E.Penner- Hahn,G.L.Verdine,G.Wagner
Key ref:
Y.Lin et al. (2001). Structural basis for the functional switch of the E. coli Ada protein. Biochemistry, 40, 4261-4271. PubMed id: 11284682 DOI: 10.1021/bi002109p
Date:
06-May-00     Release date:   09-Sep-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P06134  (ADA_ECOLI) -  Bifunctional transcriptional activator/DNA repair enzyme Ada
Seq:
Struc:
354 a.a.
92 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: E.C.2.1.1  - Guanidinoacetate N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Creatine Biosynthesis
      Reaction: S-adenosyl-L-methionine + guanidinoacetate = S-adenosyl-L-homocysteine + creatine
S-adenosyl-L-methionine
+ guanidinoacetate
= S-adenosyl-L-homocysteine
+ creatine
   Enzyme class 2: E.C.2.1.1.63  - Methylated-DNA--[protein]-cysteine S-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine
DNA (containing 6-O-methylguanine)
+ protein L-cysteine
= DNA (without 6-O-methylguanine)
+ protein S-methyl-L-cysteine
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     DNA repair   2 terms 
  Biochemical function     DNA binding     3 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi002109p Biochemistry 40:4261-4271 (2001)
PubMed id: 11284682  
 
 
Structural basis for the functional switch of the E. coli Ada protein.
Y.Lin, V.Dötsch, T.Wintner, K.Peariso, L.C.Myers, J.E.Penner-Hahn, G.L.Verdine, G.Wagner.
 
  ABSTRACT  
 
The Escherichia coli protein Ada specifically repairs the S(p) diastereomer of DNA methyl phosphotriesters in DNA by direct and irreversible transfer of the methyl group to its own Cys 69 which is part of a zinc-thiolate center. The methyl transfer converts Ada into a transcriptional activator that binds sequence-specifically to promoter regions of its own gene and other methylation resistance genes. Ada thus acts as a chemosensor to activate repair mechanisms in situations of methylation damage. Here we present a highly refined solution structure of the 10 kDa N-terminal domain, N-Ada10, which reveals structural details of the nonspecific DNA interaction of N-Ada10 during the repair process and provides a basis for understanding the mechanism of the conformational switch triggered by methyl transfer. To further elucidate this, EXAFS (extended X-ray absorption fine structure) and XANES (X-ray absorption near-edge structure) data were acquired, which confirmed that the zinc-thiolate center is maintained when N-Ada is methylated. Thus, ligand exchange is not the mechanism that enhances sequence-specific DNA binding and transcriptional activation upon methylation of N-Ada. The mechanism of the switch was further elucidated by recording NOESY spectra of specifically labeled methylated-Ada/DNA complexes, which showed that the transferred methyl group makes many contacts within N-Ada but none with the DNA. This implies that methylation of N-Ada induces a structural change, which enhances the promoter affinity of a remodeled surface region that does not include the transferred methyl group.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
17376731 J.Penner-Hahn (2007).
Zinc-promoted alkyl transfer: a new role for zinc.
  Curr Opin Chem Biol, 11, 166-171.  
16452614 H.Takinowaki, Y.Matsuda, T.Yoshida, Y.Kobayashi, and T.Ohkubo (2006).
The solution structure of the methylated form of the N-terminal 16-kDa domain of Escherichia coli Ada protein.
  Protein Sci, 15, 487-497.
PDB code: 1wpk
16464003 Y.Mishina, E.M.Duguid, and C.He (2006).
Direct reversal of DNA alkylation damage.
  Chem Rev, 106, 215-232.  
16209950 C.He, J.C.Hus, L.J.Sun, P.Zhou, D.P.Norman, V.Dötsch, H.Wei, J.D.Gross, W.S.Lane, G.Wagner, and G.L.Verdine (2005).
A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada.
  Mol Cell, 20, 117-129.
PDB codes: 1u8b 1zgw
15040447 B.Sedgwick (2004).
Repairing DNA-methylation damage.
  Nat Rev Mol Cell Biol, 5, 148-157.  
12649324 S.J.Chiou, C.G.Riordan, and A.L.Rheingold (2003).
Synthetic modeling of zinc thiolates: quantitative assessment of hydrogen bonding in modulating sulfur alkylation rates.
  Proc Natl Acad Sci U S A, 100, 3695-3700.  
12220488 J.C.Evans, D.P.Huddler, J.Jiracek, C.Castro, N.S.Millian, T.A.Garrow, and M.L.Ludwig (2002).
Betaine-homocysteine methyltransferase: zinc in a distorted barrel.
  Structure, 10, 1159-1171.
PDB codes: 1lt7 1lt8
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.