PDBsum entry 1p7m

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Hydrolase PDB id
Protein chain
187 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Solution structure and base perturbation studies reveal a novel mode of alkylated base recognition by 3- methyladenine DNA glycosylase i
Structure: DNA-3-methyladenine glycosylase i. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: tag or b3549. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 25 models
Authors: C.Cao,K.Kwon,Y.L.Jiang,A.C.Drohat,J.T.Stivers
Key ref:
C.Cao et al. (2003). Solution structure and base perturbation studies reveal a novel mode of alkylated base recognition by 3-methyladenine DNA glycosylase I. J Biol Chem, 278, 48012-48020. PubMed id: 13129925 DOI: 10.1074/jbc.M307500200
02-May-03     Release date:   25-Nov-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P05100  (3MG1_ECOLI) -  DNA-3-methyladenine glycosylase 1
187 a.a.
187 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - DNA-3-methyladenine glycosylase I.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of alkylated DNA, releasing 3-methyladenine.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     response to DNA damage stimulus   4 terms 
  Biochemical function     catalytic activity     4 terms  


DOI no: 10.1074/jbc.M307500200 J Biol Chem 278:48012-48020 (2003)
PubMed id: 13129925  
Solution structure and base perturbation studies reveal a novel mode of alkylated base recognition by 3-methyladenine DNA glycosylase I.
C.Cao, K.Kwon, Y.L.Jiang, A.C.Drohat, J.T.Stivers.
The specific recognition mechanisms of DNA repair glycosylases that remove cationic alkylpurine bases in DNA are not well understood partly due to the absence of structures of these enzymes with their cognate bases. Here we report the solution structure of 3-methyladenine DNA glycosylase I (TAG) in complex with its 3-methyladenine (3-MeA) cognate base, and we have used chemical perturbation of the base in combination with mutagenesis of the enzyme to evaluate the role of hydrogen bonding and pi-cation interactions in alkylated base recognition by this DNA repair enzyme. We find that TAG uses hydrogen bonding with heteroatoms on the base, van der Waals interactions with the 3-Me group, and conventional pi-pi stacking with a conserved Trp side chain to selectively bind neutral 3-MeA over the cationic form of the base. Discrimination against binding of the normal base adenine is derived from direct sensing of the 3-methyl group, leading to an induced-fit conformational change that engulfs the base in a box defined by five aromatic side chains. These findings indicate that base specific recognition by TAG does not involve strong pi-cation interactions, and suggest a novel mechanism for alkylated base recognition and removal.
  Selected figure(s)  
Figure 2.
FIG. 2. The 3-MeA binding pocket of TAG. A, traces of active site amino acid side chains and 3-MeA using the 10 lowest energy structures. The structures are aligned to the mean. B, the structure of the aromatic-rich base binding pocket of TAG (lowest energy structure). Each of the amino acid side chains depicted was mutated to alanine to evaluate their roles in 3-MeA recognition (see text and Fig. 4). C, molecular surface representation of the active site. The 3-MeA base is encapsulated in an aromatic box, with Trp-6 serving as the lid. An induced-fit binding mechanism is indicated, because there is no obvious path for the base to enter the aromatic box (see text). For reference, the N9 atom of the 3-MeA base is labeled, indicating that the position of the anomeric carbon of the deoxyribose sugar of the DNA substrate would be located just above this atom as shown. D, interactions with the 3-MeA base.
Figure 7.
FIG. 7. Model depicting how TAG may lower the activation barrier for glycosidic bond cleavage of 3-MeA. For a charged base, hydrogen bonding and stacking interactions that are weak or strained in the ground state become stronger in the transition state where the charge is quenched by release of the electrons in the glycosidic bond into the aromatic ring of the base. In contrast, a neutral base would bind more tightly in the ground state, and electrostatic strain would develop in the transition state as negative charge develops on the base. The net result is that the activation barrier is decreased for a cationic substrate and increased for the neutral substrate as compared with aqueous solution. This catalytic mechanism could lead to discrimination between damaged and undamaged bases.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 48012-48020) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21267490 A.Ebrahimi, M.Habibi-Khorassani, and S.Bazzi (2011).
The impact of protonation and deprotonation of 3-methyl-2'-deoxyadenosine on N-glycosidic bond cleavage.
  Phys Chem Chem Phys, 13, 3334-3343.  
17410210 A.H.Metz, T.Hollis, and B.F.Eichman (2007).
DNA damage recognition and repair by 3-methyladenine DNA glycosylase I (TAG).
  EMBO J, 26, 2411-2420.
PDB codes: 2ofi 2ofk
17395642 B.Dalhus, I.H.Helle, P.H.Backe, I.Alseth, T.Rognes, M.Bjørås, and J.K.Laerdahl (2007).
Structural insight into repair of alkylated DNA by a new superfamily of DNA glycosylases comprising HEAT-like repeats.
  Nucleic Acids Res, 35, 2451-2459.  
16984202 M.T.Bennett, M.T.Rodgers, A.S.Hebert, L.E.Ruslander, L.Eisele, and A.C.Drohat (2006).
Specificity of human thymine DNA glycosylase depends on N-glycosidic bond stability.
  J Am Chem Soc, 128, 12510-12519.  
15558051 C.Cao, Y.L.Jiang, J.T.Stivers, and F.Song (2004).
Dynamic opening of DNA during the enzymatic search for a damaged base.
  Nat Struct Mol Biol, 11, 1230-1236.  
15102448 J.C.Fromme, A.Banerjee, and G.L.Verdine (2004).
DNA glycosylase recognition and catalysis.
  Curr Opin Struct Biol, 14, 43-49.  
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