Enhanced resolution of molecular recognition to distinguish structurally similar molecules by different conformational responses of a protein upon ligand binding

Higuchi, Makie; Fujii, Jumpei; Yonetani, Yoshiteru; Kitao, Akio; Gō, Nobuhiro

doi:10.1016/j.jsb.2010.09.022

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…These structures have revealed that MutT specifically recognizes 8-oxoguanine nucleotides through a number of hydrogen bonds by a ligand-binding-induced conformational change (Nakamura et al, 2010). These features are supported by the molecular-dynamics simulation method (Higuchi et al, 2011). As previously mentioned, hMTH1 has a broad substrate specificity for several oxidized purine nucleotides (Fujikawa et al, 1999(Fujikawa et al, , 2001.…”

Section: Introductionsupporting

confidence: 58%

Crystallization and preliminary X-ray analysis of human MTH1 with a homogeneous N-terminus

et al. 2012

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Human MTH1 (hMTH1) is an enzyme that hydrolyses several oxidized purine nucleoside triphosphates to their corresponding nucleoside monophosphates. Crystallographic studies have shown that the accurate mode of interaction between 8-oxoguanine and hMTH1 cannot be understood without determining the positions of the H atoms, as can be observed in neutron and/or ultrahigh-resolution X-ray diffraction studies. The hMTH1 protein prepared in the original expression system from Escherichia coli did not appear to be suitable for obtaining high-quality crystals because the hMTH1 protein had heterogeneous N-termini of Met1 and Gly2 that resulted from N-terminal Met excision by methionine aminopeptidase from the E. coli host. To obtain homogeneous hMTH1, the Gly at the second position was replaced by Lys. As a result, mutant hMTH1 protein [hMTH1(G2K)] with a homogeneous N-terminus could be prepared and high-quality crystals which diffracted to near 1.1 Å resolution using synchrotron radiation were produced. The new crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 46.36, b = 47.58, c = 123.89 Å.

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Section: Introductionsupporting

confidence: 58%

Crystallization and preliminary X-ray analysis of human MTH1 with a homogeneous N-terminus

et al. 2012

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“…The much better nucleotide coordination and the similarity with the structure of the human enzyme (see below) indicate that the crystal structure but not the NMR structures faithfully describes the MutT/substrate complex. Molecular dynamics studies [161] suggest that the high specificity of MutT for the damaged dNTP (ksp oxoG/ksp G ~6000 [162]) is partially due to a change in the enzyme conformation upon substrate binding that is more favorable for oxodGTP than for dGTP. Unexpectedly for a seemingly important substrate-recognizing residue, Asn119 is not conserved in the MutT family (changed to Asp in many sequences) and the MTH1 family uniformly contains Asp in this position.…”

Section: Mutt and Mth1 (Nudt1)mentioning

confidence: 99%

Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase

et al. 2019

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7,8-Dihydro-8-oxoguanine (oxoG) is the most abundant oxidative DNA lesion with dual coding properties. It forms both Watson–Crick (anti)oxoG:(anti)C and Hoogsteen (syn)oxoG:(anti)A base pairs without a significant distortion of a B-DNA helix. DNA polymerases bypass oxoG but the accuracy of nucleotide incorporation opposite the lesion varies depending on the polymerase-specific interactions with the templating oxoG and incoming nucleotides. High-fidelity replicative DNA polymerases read oxoG as a cognate base for A while treating oxoG:C as a mismatch. The mutagenic effects of oxoG in the cell are alleviated by specific systems for DNA repair and nucleotide pool sanitization, preventing mutagenesis from both direct DNA oxidation and oxodGMP incorporation. DNA translesion synthesis could provide an additional protective mechanism against oxoG mutagenesis in cells. Several human DNA polymerases of the X- and Y-families efficiently and accurately incorporate nucleotides opposite oxoG. In this review, we address the mutagenic potential of oxoG in cells and discuss the structural basis for oxoG bypass by different DNA polymerases and the mechanisms of the recognition of oxoG by DNA glycosylases and dNTP hydrolases.

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Enhanced resolution of molecular recognition to distinguish structurally similar molecules by different conformational responses of a protein upon ligand binding

Cited by 2 publications

References 21 publications

Crystallization and preliminary X-ray analysis of human MTH1 with a homogeneous N-terminus

Crystallization and preliminary X-ray analysis of human MTH1 with a homogeneous N-terminus

Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase

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