3zr0
From Proteopedia
CRYSTAL STRUCTURE OF HUMAN MTH1 IN COMPLEX WITH 8-OXO-DGMP
Structural highlights
Function[8ODP_HUMAN] Antimutagenic. Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress. Hydrolyzes 8-oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions. Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8-oxo-GTP and 8-oxo-ATP.[1] [2] [3] [4] [5] Publication Abstract from PubMedMTH1 hydrolyzes oxidized nucleotide triphosphates, thereby preventing them from being incorporated into DNA. We here present the structures of human MTH1 (1.9A) and its complex with the product 8-oxo-dGMP (1.8A). 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. Crystal structure of human MTH1 and the 8-oxo-dGMP product complex.,Svensson LM, Jemth AS, Desroses M, Loseva O, Helleday T, Hogbom M, Stenmark P FEBS Lett. 2011 Aug 19;585(16):2617-21. Epub 2011 Jul 23. PMID:21787772[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Desroses, M | Helleday, T | Hogbom, M | Jemth, A | Loseva, O | Stenmark, P | Svensson, L M | Dna repair | Hydrolase
