Houten S M, Waterham H R
Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Mol Genet Metab. 2001 Mar;72(3):273-6. doi: 10.1006/mgme.2000.3133.
Phosphomevalonate kinase (PMK; EC 2.7.4.2) catalyzes the phosphorylation of 5-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.
磷酸甲羟戊酸激酶（PMK；EC 2.7.4.2）催化5-磷酸甲羟戊酸磷酸化生成5-二磷酸甲羟戊酸，这是甲羟戊酸途径中类异戊二烯生物合成的关键步骤。到目前为止，已经描述了两个编码PMK的非直系同源基因，即酿酒酵母ERG8基因和人类PMK基因。在此，我们报告ERG8的直系同源基因存在于真细菌、真菌和植物中，而人类PMK的直系同源基因仅在动物中发现，这表明在动物进化早期发生了非直系同源基因替代。这也反映在不同的共有ATP结合基序上：ERG8直系同源基因中的蛋白激酶基序与动物直系同源基因中的P环或沃克A基序。ERG8直系同源基因存在于致病性真细菌和真菌中但不存在于人类中，这一事实使其成为开发抗菌和/或抗真菌药物的有吸引力的靶点。
