2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase

Details

Name
2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
Synonyms
  • 4.6.1.12
  • MECDP-synthase
  • mecS
  • ygbB
Gene Name
ispF
Organism
Escherichia coli (strain K12)
Amino acid sequence
>lcl|BSEQ0012860|2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
MRIGHGFDVHAFGGEGPIIIGGVRIPYEKGLLAHSDGDVALHALTDALLGAAALGDIGKL
FPDTDPAFKGADSRELLREAWRRIQAKGYTLGNVDVTIIAQAPKMLPHIPQMRVFIAEDL
GCHMDDVNVKATTTEKLGFTGRGEGIACEAVALLIKATK
Number of residues
159
Molecular Weight
16897.37
Theoretical pI
6.51
GO Classification
Functions
2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity / identical protein binding / manganese ion binding / metal ion binding / zinc ion binding
Processes
isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway / terpenoid biosynthetic process / ubiquinone biosynthetic process
General Function
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.
Specific Function
2-c-methyl-d-erythritol 2,4-cyclodiphosphate synthase activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0012861|2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (ispF)
ATGCGAATTGGACACGGTTTTGACGTACATGCCTTTGGCGGTGAAGGCCCAATTATCATT
GGTGGCGTACGCATTCCTTACGAAAAAGGATTGCTGGCGCATTCTGATGGCGACGTGGCG
CTCCATGCGTTGACCGATGCATTGCTTGGCGCGGCGGCGCTGGGGGATATCGGCAAGCTG
TTCCCGGATACCGATCCGGCATTTAAAGGTGCCGATAGCCGCGAGCTGCTACGCGAAGCC
TGGCGTCGTATTCAGGCGAAGGGTTATACCCTTGGCAACGTCGATGTCACTATCATCGCT
CAGGCACCGAAGATGTTGCCGCACATTCCACAAATGCGCGTGTTTATTGCCGAAGATCTC
GGCTGCCATATGGATGATGTTAACGTGAAAGCCACTACTACGGAAAAACTGGGATTTACC
GGACGTGGGGAAGGGATTGCCTGTGAAGCGGTGGCGCTACTCATTAAGGCAACAAAATGA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP62617
UniProtKB Entry NameISPF_ECOLI
GenBank Protein ID433711
GenBank Gene IDL07942
General References
  1. Li C, Ichikawa JK, Ravetto JJ, Kuo HC, Fu JC, Clarke S: A new gene involved in stationary-phase survival located at 59 minutes on the Escherichia coli chromosome. J Bacteriol. 1994 Oct;176(19):6015-22. [Article]
  2. 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. [Article]
  3. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. [Article]
  4. Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. Epub 2006 Feb 21. [Article]
  5. Fountoulakis M, Takacs MF, Berndt P, Langen H, Takacs B: Enrichment of low abundance proteins of Escherichia coli by hydroxyapatite chromatography. Electrophoresis. 1999 Aug;20(11):2181-95. [Article]
  6. Campbell TL, Brown ED: Characterization of the depletion of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate synthase in Escherichia coli and Bacillus subtilis. J Bacteriol. 2002 Oct;184(20):5609-18. [Article]
  7. 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. [Article]
  8. Richard SB, Ferrer JL, Bowman ME, Lillo AM, Tetzlaff CN, Cane DE, Noel JP: Structure and mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase. An enzyme in the mevalonate-independent isoprenoid biosynthetic pathway. J Biol Chem. 2002 Mar 8;277(10):8667-72. Epub 2002 Jan 10. [Article]
  9. 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. [Article]
  10. Kemp LE, Bond CS, Hunter WN: Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development. Proc Natl Acad Sci U S A. 2002 May 14;99(10):6591-6. Epub 2002 May 7. [Article]
  11. Kemp LE, Alphey MS, Bond CS, Ferguson MA, Hecht S, Bacher A, Eisenreich W, Rohdich F, Hunter WN: The identification of isoprenoids that bind in the intersubunit cavity of Escherichia coli 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase by complementary biophysical methods. Acta Crystallogr D Biol Crystallogr. 2005 Jan;61(Pt 1):45-52. Epub 2004 Dec 17. [Article]
  12. Sgraja T, Kemp LE, Ramsden N, Hunter WN: A double mutation of Escherichia coli2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase disrupts six hydrogen bonds with, yet fails to prevent binding of, an isoprenoid diphosphate. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jul 1;61(Pt 7):625-9. Epub 2005 Jun 30. [Article]
  13. Crane CM, Kaiser J, Ramsden NL, Lauw S, Rohdich F, Eisenreich W, Hunter WN, Bacher A, Diederich F: Fluorescent inhibitors for IspF, an enzyme in the non-mevalonate pathway for isoprenoid biosynthesis and a potential target for antimalarial therapy. Angew Chem Int Ed Engl. 2006 Feb 6;45(7):1069-74. [Article]
  14. Ramsden NL, Buetow L, Dawson A, Kemp LA, Ulaganathan V, Brenk R, Klebe G, Hunter WN: A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy. J Med Chem. 2009 Apr 23;52(8):2531-42. doi: 10.1021/jm801475n. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02552Geranyl DiphosphateexperimentalunknownDetails