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Publication Abstract from PubMed

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 (AiPEPCK) at 2.6 A 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 and to determine the structural basis for the PPi specificity of PPi-type PEPCKs. These comparisons revealed that the amino acid residues directly contributing to substrate recognition, except for those that recognize purine moieties, are conserved. Furthermore, the order of secondary structure 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 for PPi specificity and suggest that all of these PEPCKs are derived from a common ancestor.

Structural comparisons of phosphoenolpyruvate carboxykinases reveal the evolutionary trajectories of these phosphodiester energy-conversion enzymes.,Chiba Y, Miyakawa T, Shimane Y, Takai K, Tanokura M, Nozaki T J Biol Chem. 2019 Oct 28. pii: RA119.010920. doi: 10.1074/jbc.RA119.010920. PMID:31662435^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.