RRC ID 57725
Author Chiba Y, Miyakawa T, Shimane Y, Takai K, Tanokura M, Nozaki T.
Title Structural comparisons of phosphoenolpyruvate carboxykinases reveal the evolutionary trajectories of these phosphodiester energy conversion enzymes.
Journal J Biol Chem
Abstract Inorganic pyrophosphate (PPi) consists of two phosphate molecules and can act as an energy and phosphate donor in cellular reactions, similar to ATP. Several kinases use PPi as a substrate, and these kinases have recently been suggested to have evolved from ATP-dependent functional homologs, which have significant amino acid sequence similarity to PPi-utilizing enzymes. In contrast, phosphoenolpyruvate carboxykinase (PEPCK) can be divided into three types according to the phosphate donor (ATP, GTP, or PPi), and the amino acid sequence similarity of these PEPCKs is too low to confirm that they share a common ancestor. Here we solved the crystal structure of a PPi-PEPCK homolog from the bacterium Actinomyces israelii at 2.6 Å resolution and compared it with previously reported structures from ATP- and GTP-specific PEPCKs to assess the degrees of similarities and divergences among these PEPCKs. These comparisons revealed that they share a tertiary structure with significant value and that amino acid residues directly contributing to substrate recognition, except for those that recognize purine moieties, are conserved. Furthermore, the order of secondary structural elements between PPi-, ATP-, and GTP-specific PEPCKs was strictly conserved. The structure-based comparisons of the three PEPCK types provide key insights into the structural basis of PPi specificity and suggest that all of these PEPCKs are derived from a common ancestor.
Volume 294(50)
Pages 19269-19278
Published 2019-12-13
DOI 10.1074/jbc.RA119.010920
PII RA119.010920
PMID 31662435
PMC PMC6916476
MeSH Diphosphates / chemistry Diphosphates / metabolism* Humans Models, Molecular Phosphoenolpyruvate Carboxylase / chemistry Phosphoenolpyruvate Carboxylase / metabolism* Protein Conformation
IF 4.238
Times Cited 0
DNA material Genomic DNA of Actinomyces israelii JCM 12964 T (JGD12771)