Common hydrogen bond interactions in diverse phosphoryl transfer active sites

Jean C. Summerton, Gregory M. Martin, Jeffrey D. Evanseck, Michael S. Chapman

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Phosphoryl transfer reactions figure prominently in energy metabolism, signaling, transport and motility. Prior detailed studies of selected systems have highlighted mechanistic features that distinguish different phosphoryl transfer enzymes. Here, a top-down approach is developed for comparing statistically the active site configurations between populations of diverse structures in the Protein Data Bank, and it reveals patterns of hydrogen bonding that transcend enzyme families. Through analysis of large samples of structures, insights are drawn at a level of detail exceeding the experimental precision of an individual structure. In phosphagen kinases, for example, hydrogen bonds with the O3b of the nucleotide substrate are revealed as analogous to those in unrelated G proteins. In G proteins and other enzymes, interactions with O3b have been understood in terms of electrostatic favoring of the transition state. Ground state quantum mechanical calculations on model compounds show that the active site interactions highlighted in our database analysis can affect substrate phosphate charge and bond length, in ways that are consistent with prior experimental observations, by modulating hyperconjugative orbital interactions that weaken the scissile bond. Testing experimentally the inference about the importance of Ointeractions in phosphagen kinases, mutation of arginine kinase Arg280decreases kcat, as predicted, with little impact upon KM.

Original languageEnglish (US)
Article numbere108310
JournalPloS one
Issue number9
StatePublished - Sep 19 2014
Externally publishedYes

ASJC Scopus subject areas

  • General


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