4-hydroxy-3-methylbut-2-enyl diphosphate reductase

Details

Name
4-hydroxy-3-methylbut-2-enyl diphosphate reductase
Synonyms
  • 1.17.1.2
  • lytB
  • yaaE
Gene Name
ispH
Organism
Escherichia coli (strain K12)
Amino acid sequence
>lcl|BSEQ0019513|4-hydroxy-3-methylbut-2-enyl diphosphate reductase
MQILLANPRGFCAGVDRAISIVENALAIYGAPIYVRHEVVHNRYVVDSLRERGAIFIEQI
SEVPDGAILIFSAHGVSQAVRNEAKSRDLTVFDATCPLVTKVHMEVARASRRGEESILIG
HAGHPEVEGTMGQYSNPEGGMYLVESPDDVWKLTVKNEEKLSFMTQTTLSVDDTSDVIDA
LRKRFPKIVGPRKDDICYATTNRQEAVRALAEQAEVVLVVGSKNSSNSNRLAELAQRMGK
RAFLIDDAKDIQEEWVKEVKCVGVTAGASAPDILVQNVVARLQQLGGGEAIPLEGREENI
VFEVPKELRVDIREVD
Number of residues
316
Molecular Weight
34774.275
Theoretical pI
4.95
GO Classification
Functions
3 iron, 4 sulfur cluster binding / 4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase activity / hydroxymethylbutenyl pyrophosphate reductase activity / metal ion binding
Processes
dimethylallyl diphosphate biosynthetic process / isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway / terpenoid biosynthetic process
Components
cytosol
General Function
Metal ion binding
Specific Function
Converts 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Is also involved in penicillin tolerance and control of the stringent response. Seems to directly or indirectly interact with RelA to maintain it in an inactive form during normal growth.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0019514|4-hydroxy-3-methylbut-2-enyl diphosphate reductase (ispH)
ATGCAGATCCTGTTGGCCAACCCGCGTGGTTTTTGTGCCGGGGTAGACCGCGCTATCAGC
ATTGTTGAAAACGCGCTGGCCATTTACGGCGCACCGATATATGTCCGTCACGAAGTGGTA
CATAACCGCTATGTGGTCGATAGCTTGCGTGAGCGTGGGGCTATCTTTATTGAGCAGATT
AGCGAAGTACCGGACGGCGCGATCCTGATTTTCTCCGCACACGGTGTTTCTCAGGCGGTA
CGTAACGAAGCAAAAAGTCGCGATTTGACGGTGTTTGATGCCACCTGTCCGCTGGTGACC
AAAGTGCATATGGAAGTCGCCCGCGCCAGTCGCCGTGGCGAAGAATCTATTCTCATCGGT
CACGCCGGGCACCCGGAAGTGGAAGGGACAATGGGCCAGTACAGTAACCCGGAAGGGGGA
ATGTATCTGGTCGAATCGCCGGACGATGTGTGGAAACTGACGGTCAAAAACGAAGAGAAG
CTCTCCTTTATGACCCAGACCACGCTGTCGGTGGATGACACGTCTGATGTGATCGACGCG
CTGCGTAAACGCTTCCCGAAAATTGTCGGTCCGCGCAAAGATGACATCTGCTACGCCACG
ACTAACCGTCAGGAAGCGGTACGCGCCCTGGCAGAACAGGCGGAAGTTGTGTTGGTGGTC
GGTTCGAAAAACTCCTCCAACTCCAACCGTCTGGCGGAGCTGGCCCAGCGTATGGGCAAA
CGCGCGTTTTTGATTGACGATGCGAAAGACATCCAGGAAGAGTGGGTGAAAGAGGTTAAA
TGCGTCGGCGTGACTGCGGGCGCATCGGCTCCGGATATTCTGGTGCAGAATGTGGTGGCA
CGTTTGCAGCAGCTGGGCGGTGGTGAAGCCATTCCGCTGGAAGGCCGTGAAGAAAACATT
GTTTTCGAAGTGCCGAAAGAGCTGCGTGTCGATATTCGTGAAGTCGATTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP62623
UniProtKB Entry NameISPH_ECOLI
GenBank Protein ID18652795
GenBank Gene IDAY062212
General References
  1. Rohdich F, Hecht S, Gartner K, Adam P, Krieger C, Amslinger S, Arigoni D, Bacher A, Eisenreich W: Studies on the nonmevalonate terpene biosynthetic pathway: metabolic role of IspH (LytB) protein. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1158-63. Epub 2002 Jan 29. [PubMed:11818558]
  2. Bouvier J, Stragier P: Nucleotide sequence of the lsp-dapB interval in Escherichia coli. Nucleic Acids Res. 1991 Jan 11;19(1):180. [PubMed:2011499]
  3. Yura T, Mori H, Nagai H, Nagata T, Ishihama A, Fujita N, Isono K, Mizobuchi K, Nakata A: Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region. Nucleic Acids Res. 1992 Jul 11;20(13):3305-8. [PubMed:1630901]
  4. 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. [PubMed:9278503]
  5. 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. [PubMed:16738553]
  6. Gustafson CE, Kaul S, Ishiguro EE: Identification of the Escherichia coli lytB gene, which is involved in penicillin tolerance and control of the stringent response. J Bacteriol. 1993 Feb;175(4):1203-5. [PubMed:8432714]
  7. Altincicek B, Kollas A, Eberl M, Wiesner J, Sanderbrand S, Hintz M, Beck E, Jomaa H: LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli. FEBS Lett. 2001 Jun 15;499(1-2):37-40. [PubMed:11418107]
  8. McAteer S, Coulson A, McLennan N, Masters M: The lytB gene of Escherichia coli is essential and specifies a product needed for isoprenoid biosynthesis. J Bacteriol. 2001 Dec;183(24):7403-7. [PubMed:11717301]
  9. Adam P, Hecht S, Eisenreich W, Kaiser J, Grawert T, Arigoni D, Bacher A, Rohdich F: Biosynthesis of terpenes: studies on 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12108-13. Epub 2002 Aug 27. [PubMed:12198182]
  10. Wolff M, Seemann M, Tse Sum Bui B, Frapart Y, Tritsch D, Garcia Estrabot A, Rodriguez-Concepcion M, Boronat A, Marquet A, Rohmer M: Isoprenoid biosynthesis via the methylerythritol phosphate pathway: the (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB/IspH) from Escherichia coli is a [4Fe-4S] protein. FEBS Lett. 2003 Apr 24;541(1-3):115-20. [PubMed:12706830]
  11. Rohdich F, Zepeck F, Adam P, Hecht S, Kaiser J, Laupitz R, Grawert T, Amslinger S, Eisenreich W, Bacher A, Arigoni D: The deoxyxylulose phosphate pathway of isoprenoid biosynthesis: studies on the mechanisms of the reactions catalyzed by IspG and IspH protein. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1586-91. Epub 2003 Feb 5. [PubMed:12571359]
  12. Grawert T, Kaiser J, Zepeck F, Laupitz R, Hecht S, Amslinger S, Schramek N, Schleicher E, Weber S, Haslbeck M, Buchner J, Rieder C, Arigoni D, Bacher A, Eisenreich W, Rohdich F: IspH protein of Escherichia coli: studies on iron-sulfur cluster implementation and catalysis. J Am Chem Soc. 2004 Oct 13;126(40):12847-55. [PubMed:15469281]
  13. Grawert T, Rohdich F, Span I, Bacher A, Eisenreich W, Eppinger J, Groll M: Structure of active IspH enzyme from Escherichia coli provides mechanistic insights into substrate reduction. Angew Chem Int Ed Engl. 2009;48(31):5756-9. doi: 10.1002/anie.200900548. [PubMed:19569147]
  14. Grawert T, Span I, Eisenreich W, Rohdich F, Eppinger J, Bacher A, Groll M: Probing the reaction mechanism of IspH protein by x-ray structure analysis. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1077-81. doi: 10.1073/pnas.0913045107. Epub 2009 Dec 28. [PubMed:20080550]
  15. Span I, Grawert T, Bacher A, Eisenreich W, Groll M: Crystal structures of mutant IspH proteins reveal a rotation of the substrate's hydroxymethyl group during catalysis. J Mol Biol. 2012 Feb 10;416(1):1-9. doi: 10.1016/j.jmb.2011.11.033. Epub 2011 Nov 23. [PubMed:22137895]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01785Dimethylallyl DiphosphateexperimentalunknownDetails
DB04714ISOPENTENYL PYROPHOSPHATEexperimentalunknownDetails