3A6S

Crystal structure of the MutT protein

Summary for 3A6S

• Entry DOI: 10.2210/pdb3a6s/pdb
• Related: 3A6T 3A6U 3A6V
• Descriptor: Mutator mutT protein, SODIUM ION, L(+)-TARTARIC ACID, ... (4 entities in total)
• Functional Keywords: alpha-beta-alpha sandwich, dna damage, dna repair, dna replication, hydrolase, mutator protein
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 2
• Total formula weight: 30063.14

Authors

Nakamura, T.,Yamagata, Y. (deposition date: 2009-09-09, release date: 2009-10-27, Last modification date: 2024-03-13)

Primary citation

Nakamura, T.,Meshitsuka, S.,Kitagawa, S.,Abe, N.,Yamada, J.,Ishino, T.,Nakano, H.,Tsuzuki, T.,Doi, T.,Kobayashi, Y.,Fujii, S.,Sekiguchi, M.,Yamagata, Y.
Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base
J.Biol.Chem., 285:444-452, 2010

PubMed Abstract: Escherichia coli MutT hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, an event that can prevent the misincorporation of 8-oxoguanine opposite adenine in DNA. Of the several enzymes that recognize 8-oxoguanine, MutT exhibits high substrate specificity for 8-oxoguanine nucleotides; however, the structural basis for this specificity is unknown. The crystal structures of MutT in the apo and holo forms and in the binary and ternary forms complexed with the product 8-oxo-dGMP and 8-oxo-dGMP plus Mn(2+), respectively, were determined. MutT strictly recognizes the overall conformation of 8-oxo-dGMP through a number of hydrogen bonds. This recognition mode revealed that 8-oxoguanine nucleotides are discriminated from guanine nucleotides by not only the hydrogen bond between the N7-H and Odelta (N119) atoms but also by the syn glycosidic conformation that 8-oxoguanine nucleotides prefer. Nevertheless, these discrimination factors cannot by themselves explain the roughly 34,000-fold difference between the affinity of MutT for 8-oxo-dGMP and dGMP. When the binary complex of MutT with 8-oxo-dGMP is compared with the ligand-free form, ordering and considerable movement of the flexible loops surrounding 8-oxo-dGMP in the binary complex are observed. These results indicate that MutT specifically recognizes 8-oxoguanine nucleotides by the ligand-induced conformational change.

PubMed: 19864691
DOI: 10.1074/jbc.M109.066373

Experimental method

X-RAY DIFFRACTION (1.8 Å)