1oj4
TERNARY COMPLEX OF 4-DIPHOSPHOCYTIDYL-2-C-METHYL-D-ERYTHRITOL KINASE
|
OverviewOverview
4-Diphosphocytidyl-2C-methyl-d-erythritol kinase, an essential enzyme in, the nonmevalonate pathway of isopentenyl diphosphate and dimethylallyl, diphosphate biosynthesis, catalyzes the single ATP-dependent, phosphorylation stage affording, 4-diphosphocytidyl-2C-methyl-d-erythritol-2-phosphate. The 2-A resolution, crystal structure of the Escherichia coli enzyme in a ternary complex with, substrate and a nonhydrolyzable ATP analogue reveals the molecular, determinants of specificity and catalysis. The enzyme subunit displays the, alpha/beta fold characteristic of the galactose kinase/homoserine, kinase/mevalonate kinase/phosphomevalonate kinase superfamily, arranged, into cofactor and substrate-binding domains with the catalytic center, positioned in a deep cleft between domains. Comparisons with related, members of this superfamily indicate that the core regions of each domain, are conserved, whereas there are significant differences in the, substrate-binding pockets. The nonmevalonate pathway is essential in many, microbial pathogens and distinct from the mevalonate pathway used by, mammals. The high degree of sequence conservation of the enzyme across, bacterial species suggests similarities in structure, specificity, and, mechanism. Our model therefore provides an accurate template to facilitate, the structure-based design of broad-spectrum antimicrobial agents.
About this StructureAbout this Structure
1OJ4 is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase, with EC number 2.7.1.148 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Biosynthesis of isoprenoids: crystal structure of 4-diphosphocytidyl-2C-methyl-D-erythritol kinase., Miallau L, Alphey MS, Kemp LE, Leonard GA, McSweeney SM, Hecht S, Bacher A, Eisenreich W, Rohdich F, Hunter WN, Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9173-8. Epub 2003 Jul 23. PMID:12878729
Page seeded by OCA on Sun Feb 3 09:58:46 2008