Structural highlights
Function
ISPF_ECOLI Involved in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), two major building blocks of isoprenoid compounds. Catalyzes the conversion of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine 5-monophosphate (CMP). Also converts 4-diphosphocytidyl-2-C-methyl-D-erythritol into 2-C-methyl-D-erythritol 3,4-cyclophosphate and CMP.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Isoprenoids are biosynthesized from isopentenyl diphosphate and the isomeric dimethylallyl diphosphate via the mevalonate pathway or a mevalonate-independent pathway that was identified during the last decade. The non-mevalonate pathway is present in many bacteria, some algae and in certain protozoa such as the malaria parasite Plasmodium falciparum and in the plastids of higher plants, but not in mammals and archaea. Therefore, these enzymes have been recognised as promising drug targets. We report the crystal structure of Escherichia coli 2C- methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), which converts 4-diphosphocytidyl-2C-methyl-d-erythritol 2-phosphate into 2C-methyl-d-erythritol 2,4-cyclodiphosphate and CMP in a Mg-dependent reaction. The protein forms homotrimers that tightly bind one zinc ion per subunit at the active site, which helps to position the substrate for direct attack of the 2-phosphate group on the beta-phosphate.
Structure of 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids.,Steinbacher S, Kaiser J, Wungsintaweekul J, Hecht S, Eisenreich W, Gerhardt S, Bacher A, Rohdich F J Mol Biol. 2002 Feb 8;316(1):79-88. PMID:11829504[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Herz S, Wungsintaweekul J, Schuhr CA, Hecht S, Luttgen H, Sagner S, Fellermeier M, Eisenreich W, Zenk MH, Bacher A, Rohdich F. Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate to 2C-methyl-D-erythritol 2,4-cyclodiphosphate. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2486-90. PMID:10694574 doi:http://dx.doi.org/10.1073/pnas.040554697
- ↑ Bitok JK, Meyers CF. 2C-Methyl-d-erythritol 4-phosphate enhances and sustains cyclodiphosphate synthase IspF activity. ACS Chem Biol. 2012 Oct 19;7(10):1702-10. doi: 10.1021/cb300243w. Epub 2012 Aug, 6. PMID:22839733 doi:http://dx.doi.org/10.1021/cb300243w
- ↑ Steinbacher S, Kaiser J, Wungsintaweekul J, Hecht S, Eisenreich W, Gerhardt S, Bacher A, Rohdich F. Structure of 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids. J Mol Biol. 2002 Feb 8;316(1):79-88. PMID:11829504 doi:10.1006/jmbi.2001.5341
