5YSP

Pyrophosphate-dependent kinase in the ribokinase family complexed with a pyrophosphate analog and myo-inositol

Summary for 5YSP

• Entry DOI: 10.2210/pdb5ysp/pdb
• Descriptor: TM0415, 1,2,3,4,5,6-HEXAHYDROXY-CYCLOHEXANE, METHYLENEDIPHOSPHONIC ACID, ... (6 entities in total)
• Functional Keywords: transferase
• Biological source: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
• Total number of polymer chains: 2
• Total formula weight: 64865.99

Authors

Nagata, R.,Fujihashi, M.,Miki, K. (deposition date: 2017-11-14, release date: 2018-05-16, Last modification date: 2023-11-22)

Primary citation

Nagata, R.,Fujihashi, M.,Sato, T.,Atomi, H.,Miki, K.
Identification of a pyrophosphate-dependent kinase and its donor selectivity determinants.
Nat Commun, 9:1765-1765, 2018

PubMed Abstract: 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.

PubMed: 29720581
DOI: 10.1038/s41467-018-04201-z

Experimental method

X-RAY DIFFRACTION (1.7 Å)