6HDE

Structure of Escherichia coli dUTPase Q93H mutant

6HDE の概要

• エントリーDOI: 10.2210/pdb6hde/pdb
• 分子名称: Deoxyuridine 5'-triphosphate nucleotidohydrolase, 2'-DEOXYURIDINE 5'-ALPHA,BETA-IMIDO-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: dutpase, homotrimer, mutant, hydrolase
• 由来する生物種: Escherichia coli (strain K12)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 50412.28

構造登録者

Benedek, A.,Vertessy, B.G.,Leveles, I. (登録日: 2018-08-17, 公開日: 2019-08-28, 最終更新日: 2024-01-17)

主引用文献

Benedek, A.,Temesvary-Kis, F.,Khatanbaatar, T.,Leveles, I.,Suranyi, E.V.,Szabo, J.E.,Wunderlich, L.,Vertessy, B.G.
The Role of a Key Amino Acid Position in Species-Specific Proteinaceous dUTPase Inhibition.
Biomolecules, 9:-, 2019

PubMed Abstract: Protein inhibitors of key DNA repair enzymes play an important role in deciphering physiological pathways responsible for genome integrity, and may also be exploited in biomedical research. The staphylococcal repressor StlSaPIbov1 protein was described to be an efficient inhibitor of dUTPase homologues showing a certain degree of species-specificity. In order to provide insight into the inhibition mechanism, in the present study we investigated the interaction of StlSaPIbov1 and dUTPase. Although we observed a strong interaction of these proteins, unexpectedly the dUTPase was not inhibited. Seeking a structural explanation for this phenomenon, we identified a key amino acid position where specific mutations sensitized dUTPase to StlSaPIbov1 inhibition. We solved the three-dimensional (3D) crystal structure of such a mutant in complex with the substrate analogue dUPNPP and surprisingly found that the C-terminal arm of the enzyme, containing the P-loop-like motif was ordered in the structure. This segment was never localized before in any other dUTPase crystal structures. The 3D structure in agreement with solution phase experiments suggested that ordering of the flexible C-terminal segment upon substrate binding is a major factor in defining the sensitivity of dUTPase for StlSaPIbov1 inhibition.

PubMed: 31174420
DOI: 10.3390/biom9060221

実験手法

X-RAY DIFFRACTION (1.82 Å)