6HDE
Structure of Escherichia coli dUTPase Q93H mutant
Summary for 6HDE
| Entry DOI | 10.2210/pdb6hde/pdb |
| Descriptor | Deoxyuridine 5'-triphosphate nucleotidohydrolase, 2'-DEOXYURIDINE 5'-ALPHA,BETA-IMIDO-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | dutpase, homotrimer, mutant, hydrolase |
| Biological source | Escherichia coli (strain K12) |
| Total number of polymer chains | 3 |
| Total formula weight | 50412.28 |
| Authors | Benedek, A.,Vertessy, B.G.,Leveles, I. (deposition date: 2018-08-17, release date: 2019-08-28, Last modification date: 2024-01-17) |
| Primary citation | 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 Cited by 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: 31174420DOI: 10.3390/biom9060221 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.82 Å) |
Structure validation
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