1PU7

Crystal structure of H.pylori 3-methyladenine DNA glycosylase (MagIII) bound to 3,9-dimethyladenine

Summary for 1PU7

• Entry DOI: 10.2210/pdb1pu7/pdb
• Related: 1PU6 1PU8
• Descriptor: 3-METHYLADENINE DNA GLYCOSYLASE, 6-AMINO-3,9-DIMETHYL-9H-PURIN-3-IUM, BETA-MERCAPTOETHANOL, ... (4 entities in total)
• Functional Keywords: helix-hairpin-helix, 3-methyladenine, base excision repair, glycosylase, hydrolase
• Biological source: Helicobacter pylori
• Total number of polymer chains: 2
• Total formula weight: 50920.77

Authors

Eichman, B.F.,O'Rourke, E.J.,Radicella, J.P.,Ellenberger, T. (deposition date: 2003-06-24, release date: 2003-10-07, Last modification date: 2023-11-15)

Primary citation

Eichman, B.F.,O'Rourke, E.J.,Radicella, J.P.,Ellenberger, T.
Crystal structures of 3-methyladenine DNA glycosylase MagIII and the recognition of alkylated bases
Embo J., 22:4898-4909, 2003

PubMed Abstract: DNA glycosylases catalyze the excision of chemically modified bases from DNA. Although most glycosylases are specific to a particular base, the 3-methyladenine (m3A) DNA glycosylases include both highly specific enzymes acting on a single modified base, and enzymes with broader specificity for alkylation-damaged DNA. Our structural understanding of these different enzymatic specificities is currently limited to crystal and NMR structures of the unliganded enzymes and complexes with abasic DNA inhibitors. Presented here are high-resolution crystal structures of the m3A DNA glycosylase from Helicobacter pylori (MagIII) in the unliganded form and bound to alkylated bases 3,9-dimethyladenine and 1,N6-ethenoadenine. These are the first structures of a nucleobase bound in the active site of a m3A glycosylase belonging to the helix-hairpin-helix superfamily. MagIII achieves its specificity for positively-charged m3A not by direct interactions with purine or methyl substituent atoms, but rather by stacking the base between two aromatic side chains in a pocket that excludes 7-methylguanine. We report base excision and DNA binding activities of MagIII active site mutants, together with a structural comparison of the HhH glycosylases.

PubMed: 14517230
DOI: 10.1093/emboj/cdg505

Experimental method

X-RAY DIFFRACTION (1.93 Å)