| Type: | Family | Name: | Phosphomevalonate kinase, Gram-positive |
| Description: | This entry represents a group of predicted phosphomevalonate kinases from Gram-positive bacteria. Phosphomevalonate kinase ()catalyzes the phosphorylation of 5-phosphomevalonate into 5-diphosphomevalonate, an essential step in isoprenoid biosynthesis via the mevalonate pathway. This pathway starts with three molecules of acetyl-CoA, which, in a series of six different enzyme reactions, are converted to isopentanyl pyrophosphate (IPP), the basic C5 isoprene unit and a common intermediate for a number of pathways including isoprenoid and cholesterol biosynthesis. There are two unrelated types of PMK. The first type belongs to the GHMP kinase and includes a eukaryotic group which is typified by Saccharomyces cerevisiaeERG8 [] and a bacterial group typified by by Streptococcus pneumoniaePMK (MvaK2) []. The second type includes animal PMKs, typified by human PMK []. PMKs of the first type are present in eubacteria, fungi, and plants, while the second type is found only in animals, indicative of a nonorthologous gene displacement early in animal evolution []. PMKs of the GHMP kinase type are closely related to mevalonate kinases. The two types of PMK have different consensus ATP-binding motifs: a protein kinase motif in the ERG8 orthologs versus a P-loop or Walker A motif in the animal orthologs. The fact that ERG8 orthologs are found in pathogenic eubacteria and fungi but not in humans makes them attractive targets for the development of antibacterial and/or antifungal drugs [].This group of enzymes belongs to the GHMP kinase domain superfamily. GHMP kinases are a unique class of ATP-dependent enzymes (the abbreviation of which refers to the original members: galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase) []. Enzymes belonging to this superfamily contain three well-conserved motifs, the second of which has the typical sequence Pro-X-X-X-Gly-Leu-X-Ser-Ser-Ala and is involved in ATP binding []. The phosphate binding loop in GHMP kinases is distinct from the classical P-loops found in many ATP/GTP binding proteins. The bound ADP molecule adopts a rare syn conformation and is in the opposite orientation from those bound to the P-loop-containing proteins []. GHMP kinases display a distinctly bilobal appearance with their N-terminal subdomains dominated by a mixed beta-sheet flanked on one side by alpha-helices and their C-terminal subdomains containing a four stranded anti-parallel beta-sheet [, , , ]. | Short Name: | Pmev_kin_Gpos |
