Modeling of the enzyme-substrate complexes of human poly(ADP-ribose) polymerase 1статья
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Дата последнего поиска статьи во внешних источниках: 15 апреля 2020 г.
Аннотация:Poly(ADP-ribose) polymerase 1 (PARP-1) is a key DNA repair enzyme and an important target in cancer treatment. Conventional methods of studying the reaction mechanism of PARP-1 have limitations because of the complex structure of PARP1 substrates; however, the necessary data can be obtained by molecular modeling. In this work, a moleculardynamics model for the PARP-1 enzyme–substrate complex containing NAD+molecule and the end of the poly(ADP-ribose) chain in the form of ADP molecule was obtained for the first time. Interactions with the active site residues havebeen characterized where Gly863, Lys903, Glu988 play a crucial role, and the SN1-like mechanism for the enzymatic ADP-ribosylation reaction has been proposed. Models of PARP-1 complexes with more sophisticated two-unit fragments of thegrowing polymer chain as well as competitive inhibitors 3-aminobenzamide and 7-methylguanine have been obtained bymolecular docking.