Nonorthologous gene displacement of phosphomevalonate kinase

Phosphomevalonate kinase (PMK; EC 2.7.4.2) catalyzes the phosphorylation of 8-phosphomevalonate into 5-diphosphomevalonate, an essential step in isoprenoid biosynthesis via the mevalonate pathway. So far, two nonorthologous genes encoding PMK have been described, the Saccharomyces cerevisiae ERG8 gene and the human PMK gene. Here, we report that orthologues of ERG8 are present in eubacteria, fungi, and plants, while orthologues of human PMK are found only in animals, indicative of a nonorthologous gene displacement early in animal evolution. This also is reflected by different consensus ATP-binding motifs: a protein kinase motif in the ERG8 orthologues versus a P-loop or Walker A motif in the animal orthologues. The fact that ERG8 orthologues are found in pathogenic eubacteria and fungi but not in man makes them attractive targets for the development of antibacterial and/or antifungal drugs. (C) 2001 Academic Press.