2KIF

Solution NMR structure of an O6-methylguanine DNA methyltransferase family protein from Vibrio parahaemolyticus. Northeast Structural Genomics Consortium target VpR247.

Summary for 2KIF

• Entry DOI: 10.2210/pdb2kif/pdb
• NMR Information: BMRB: 16272
• Descriptor: O6-methylguanine-DNA methyltransferase (1 entity in total)
• Functional Keywords: methods development, solution nmr structure, dna base repair, o6 methylguanine methyltransferase, nesg, psi-2, methyltransferase, transferase, structural genomics, protein structure initiative, northeast structural genomics consortium
• Biological source: Vibrio parahaemolyticus AQ3810
• Total number of polymer chains: 1
• Total formula weight: 12341.31

Authors

Aramini, J.M.,Belote, R.L.,Ciccosanti, C.T.,Jiang, M.,Rost, B.,Nair, R.,Swapna, G.V.T.,Acton, T.B.,Xiao, R.,Everett, J.K.,Montelione, G.T.,Northeast Structural Genomics Consortium (NESG) (deposition date: 2009-05-03, release date: 2009-06-30, Last modification date: 2024-05-22)

Primary citation

Aramini, J.M.,Tubbs, J.L.,Kanugula, S.,Rossi, P.,Ertekin, A.,Maglaqui, M.,Hamilton, K.,Ciccosanti, C.T.,Jiang, M.,Xiao, R.,Soong, T.T.,Rost, B.,Acton, T.B.,Everett, J.K.,Pegg, A.E.,Tainer, J.A.,Montelione, G.T.
Structural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein.
J.Biol.Chem., 285:13736-13741, 2010

PubMed Abstract: Alkyltransferase-like proteins (ATLs) are a novel class of DNA repair proteins related to O(6)-alkylguanine-DNA alkyltransferases (AGTs) that tightly bind alkylated DNA and shunt the damaged DNA into the nucleotide excision repair pathway. Here, we present the first structure of a bacterial ATL, from Vibrio parahaemolyticus (vpAtl). We demonstrate that vpAtl adopts an AGT-like fold and that the protein is capable of tightly binding to O(6)-methylguanine-containing DNA and disrupting its repair by human AGT, a hallmark of ATLs. Mutation of highly conserved residues Tyr(23) and Arg(37) demonstrate their critical roles in a conserved mechanism of ATL binding to alkylated DNA. NMR relaxation data reveal a role for conformational plasticity in the guanine-lesion recognition cavity. Our results provide further evidence for the conserved role of ATLs in this primordial mechanism of DNA repair.

PubMed: 20212037
DOI: 10.1074/jbc.M109.093591

Experimental method

SOLUTION NMR