Comparative analysis of active sites in P-loop nucleoside triphosphatases suggests an ancestral activation mechanism
Comparative analysis of active sites in P-loop nucleoside triphosphatases suggests an ancestral activation mechanism
Abstract P-loop nucleoside triphosphatases (NTPases) share common Walker A (P-loop) and Walker B sequence motifs and depend on activating moieties (Arg or Lys fingers or a K+ ion). In search for a common catalytic mechanism, we combined structure comparisons of active sites in major classes of P-loop NTPases with molecular dynamics (MD) simulations of the Ras GTPase, a well-studied oncoprotein. Comparative structure analysis showed that positively charged activating moieties interact with gamma-phosphate groups of NTP substrates in all major classes of P-loop NTPases. In MD simulations, interaction of the activating Arg finger with the Mg-GTP-Ras complex led to the rotation of the gamma-phosphate group by 40 degrees enabling its interaction with the backbone amide group of Gly13. In all analyzed structures, the residue that corresponds to Gly13 of Ras was in a position to stabilize gamma-phosphate after its rotation, suggesting a common ancestral activation mechanism within the entire superfamily.
Cherepanov Dmitry A.、Galperin Michael Y.、Mulkidjanian Armen Y.、Shalaeva Daria N.
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University||Semenov Institute of Chemical Physics, Russian Academy of SciencesNational Center for Biotechnology Information, National Library of Medicine, National Institutes of HealthSchool of Physics, University of Osnabr¨1ck||A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University||School of Bioengineering and Bioinformatics, Lomonosov Moscow State UniversitySchool of Physics, University of Osnabr¨1ck||A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University||School of Bioengineering and Bioinformatics, Lomonosov Moscow State University
生物化学分子生物学生物物理学
Cherepanov Dmitry A.,Galperin Michael Y.,Mulkidjanian Armen Y.,Shalaeva Daria N..Comparative analysis of active sites in P-loop nucleoside triphosphatases suggests an ancestral activation mechanism[EB/OL].(2025-03-28)[2025-05-15].https://www.biorxiv.org/content/10.1101/439992.点此复制
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