||Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants
Nagata, Ryuhei ,
Fujihashi, Masahiro ,
Sato, Takaaki ,
Atomi, HaruyukiMiki, Kunio
92018-05-02 , Springer Nature
お財布にも環境にもやさしい化学反応を発見 --新規リン酸化酵素がATPでなくピロリン酸を利用する仕組み--. 京都大学プレスリリース. 2018-05-16.
Almost all kinases utilize ATP as their phosphate donor, while a few kinases utilize pyrophosphate (PPi) instead. PPi-dependent kinases are often homologous to their ATP-dependent counterparts, but determinants of their different donor specificities remain unclear. We identify a PPi-dependent member of the ribokinase family, which differs from known PPi-dependent kinases, and elucidate its PPi-binding mode based on the crystal structures. Structural comparison and sequence alignment reveal five important residues: three basic residues specifically recognizing PPi and two large hydrophobic residues occluding a part of the ATP-binding pocket. Two of the three basic residues adapt a conserved motif of the ribokinase family for the PPi binding. Using these five key residues as a signature pattern, we discover additional PPi-specific members of the ribokinase family, and thus conclude that these residues are the determinants of PPi-specific binding. Introduction of these residues may enable transformation of ATP-dependent ribokinase family members into PPi-dependent enzymes.