Phylogenetic study of the evolution of PEP-carboxykinase

Abstract

Phosphoenolpyruvate carboxykinase (PCK) is the key enzyme to initiate the gluconeogenic pathway in vertebrates, yeast, plants and most bacteria. Nucleotide specifi city divided all PCKs into two groups. All the eukaryotic mammalian and most archaeal PCKs are GTP-specifi c. Bacterial and fungal PCKs can be ATP-or GTP-specifi c but all plant PCKs are ATPspecifi c. Amino acid sequence alignment of PCK enzymes shows that the nucleotide binding sites are somewhat conserved within each class with few exceptions that do not have any clear ATP- or GTP-specifi c binding motif. Although the active site residues are mostly conserved in all PCKs, not much signifi cant sequence homology persists between ATP- and GTPdependent PCK enzymes. There is only one planctomycetes PCK enzyme (from Cadidatus Kuenenia stuttgartiensis) that shows sequence homology with both ATP-and GTP-dependent PCKs. Phylogenetic studies have been performed to understand the evolutionary relationship of various PCKs from different sources. Based on this study a fl owchart of the evolution of PCK has been proposed.