Benedek, András and Temesváry-Kis, Fanni and Khatanbaatar, Tamjidmaa and Leveles, Ibolya and Surányi, Éva Viola and Szabó, Judit Eszter and Wunderlich, Lívius and G. Vértessy, Beáta (2019) The Role of a Key Amino Acid Position in Species-Specific Proteinaceous dUTPase Inhibition. BIOMOLECULES, 9 (6). pp. 1-15. ISSN 2218-273X
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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 Escherichia coli dUTPase. Although we observed a strong interaction of these proteins, unexpectedly the E. coli dUTPase was not inhibited. Seeking a structural explanation for this phenomenon, we identified a key amino acid position where specific mutations sensitized E. coli 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 E. coli 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 E. coli dUTPase for StlSaPIbov1 inhibition.
Item Type: | Article |
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Uncontrolled Keywords: | dUTPase; trimer; inhibition; StlSaPIbov1; crystal structure; C-terminal arm |
Subjects: | Q Science / természettudomány > QR Microbiology / mikrobiológia |
SWORD Depositor: | MTMT SWORD |
Depositing User: | MTMT SWORD |
Date Deposited: | 25 Sep 2019 14:37 |
Last Modified: | 25 Sep 2019 14:37 |
URI: | http://real.mtak.hu/id/eprint/101395 |
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