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FEBS Lett. 2011 Aug 19;585(16):2617-21. doi: 10.1016/j.febslet.2011.07.017. Epub 2011 Jul 23.

Crystal structure of human MTH1 and the 8-oxo-dGMP product complex.

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1
Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.

Abstract

MTH1 hydrolyzes oxidized nucleotide triphosphates, thereby preventing them from being incorporated into DNA. We here present the structures of human MTH1 (1.9Å) and its complex with the product 8-oxo-dGMP (1.8Å). Unexpectedly MTH1 binds the nucleotide in the anti conformation with no direct interaction between the 8-oxo group and the protein. We suggest that the specificity depends on the stabilization of an enol tautomer of the 8-oxo form of dGTP. The binding of the product induces no major structural changes. The structures reveal the mode of nucleotide binding in MTH1 and provide the structural basis for inhibitor design.

PMID:
21787772
DOI:
10.1016/j.febslet.2011.07.017
[Indexed for MEDLINE]
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