Identification
Name:4-hydroxy-3-methylbut-2-enyl diphosphate reductase
Synonyms:Not Available
Gene Name:ispH
Enzyme Class:
Biological Properties
General Function:Involved in isopentenyl diphosphate biosynthetic process, mevalonate-independent pathway
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
Cellular Location:Not Available
SMPDB Pathways:
  • Secondary metabolites: isoprenoid biosynthesis (nonmevalonate pathway) PW000975
  • Secondary metabolites: methylerythritol phosphate and polyisoprenoid biosynthesis PW000958
KEGG Pathways:
KEGG Reactions:
1.0Thumb+1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb
1.0Thumb+1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb
1.0Thumb+1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb
1.0Thumb+1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb
1.0Thumb+1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb
1.0Thumb+1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb
1.0Thumb+1.0Thumb+1.0Thumb+1.0Thumb+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb+1.0Thumb
SMPDB Reactions:
1.0Thumb+1.0Thumb+1.0NADPH+1.0Thumb1.0Thumb+1.0NADPH+1.0Isopentenyl pyrophosphate+1.0Thumb
1.01-Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate + 1.0Hydrogen ion + 1.0NADPH + 1.0NADPH → 1.0Water + 1.0NADPH + 1.0Isopentenyl pyrophosphate + 1.0Isopentenyl pyrophosphate
ReactionCard
1.0Thumb+1.0Thumb+1.0NADPH+1.0Thumb1.0Thumb+1.0Thumb+1.0Dimethylallylpyrophosphate+1.0Thumb
1.01-Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate + 1.0Hydrogen ion + 1.0NADPH + 1.0NADPH → 1.0NADP + 1.0Water + 1.0Dimethylallylpyrophosphate + 1.0Dimethylallylpyrophosphate
ReactionCard
Complex Reactions:
1.0Thumb+1.0NAD(P)(+)+1.0Thumb1.0Thumb+1.0NAD(P)H
1.0Thumb+1.0NAD(P)(+)+1.0Thumb1.0Thumb+1.0NAD(P)H
Metabolites:
ECMDB IDNameView
ECMDB214731-Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphateMetaboCard
ECMDB200201-Hydroxy-2-methyl-2-butenyl 4-diphosphateMetaboCard
ECMDB01120DimethylallylpyrophosphateMetaboCard
ECMDB21225Hydrogen ionMetaboCard
ECMDB01347Isopentenyl pyrophosphateMetaboCard
ECMDB00902NADMetaboCard
ECMDB01487NADHMetaboCard
ECMDB00217NADPMetaboCard
ECMDB04111NADPHMetaboCard
ECMDB00494WaterMetaboCard
GO Classification:
Process
carboxylic acid metabolic process
cellular metabolic process
isopentenyl diphosphate biosynthetic process, mevalonate-independent pathway
metabolic process
monocarboxylic acid metabolic process
organic acid metabolic process
oxidation reduction
oxoacid metabolic process
pyruvate metabolic process
Gene Properties
Blattner:b0029
Gene OrientationClockwise
Centisome Percentage:0.57
Left Sequence End26277
Right Sequence End27227
Gene Sequence:
>951 bp
ATGCAGATCCTGTTGGCCAACCCGCGTGGTTTTTGTGCCGGGGTAGACCGCGCTATCAGC
ATTGTTGAAAACGCGCTGGCCATTTACGGCGCACCGATATATGTCCGTCACGAAGTGGTA
CATAACCGCTATGTGGTCGATAGCTTGCGTGAGCGTGGGGCTATCTTTATTGAGCAGATT
AGCGAAGTACCGGACGGCGCGATCCTGATTTTCTCCGCACACGGTGTTTCTCAGGCGGTA
CGTAACGAAGCAAAAAGTCGCGATTTGACGGTGTTTGATGCCACCTGTCCGCTGGTGACC
AAAGTGCATATGGAAGTCGCCCGCGCCAGTCGCCGTGGCGAAGAATCTATTCTCATCGGT
CACGCCGGGCACCCGGAAGTGGAAGGGACAATGGGCCAGTACAGTAACCCGGAAGGGGGA
ATGTATCTGGTCGAATCGCCGGACGATGTGTGGAAACTGACGGTCAAAAACGAAGAGAAG
CTCTCCTTTATGACCCAGACCACGCTGTCGGTGGATGACACGTCTGATGTGATCGACGCG
CTGCGTAAACGCTTCCCGAAAATTGTCGGTCCGCGCAAAGATGACATCTGCTACGCCACG
ACTAACCGTCAGGAAGCGGTACGCGCCCTGGCAGAACAGGCGGAAGTTGTGTTGGTGGTC
GGTTCGAAAAACTCCTCCAACTCCAACCGTCTGGCGGAGCTGGCCCAGCGTATGGGCAAA
CGCGCGTTTTTGATTGACGATGCGAAAGACATCCAGGAAGAGTGGGTGAAAGAGGTTAAA
TGCGTCGGCGTGACTGCGGGCGCATCGGCTCCGGATATTCTGGTGCAGAATGTGGTGGCA
CGTTTGCAGCAGCTGGGCGGTGGTGAAGCCATTCCGCTGGAAGGCCGTGAAGAAAACATT
GTTTTCGAAGTGCCGAAAGAGCTGCGTGTCGATATTCGTGAAGTCGATTAA
Protein Properties
Pfam Domain Function:
Protein Residues:316
Protein Molecular Weight:34774
Protein Theoretical pI:5
Signaling Regions:
  • None
Transmembrane Regions:
  • None
Protein Sequence:
>4-hydroxy-3-methylbut-2-enyl diphosphate reductase
MQILLANPRGFCAGVDRAISIVENALAIYGAPIYVRHEVVHNRYVVDSLRERGAIFIEQI
SEVPDGAILIFSAHGVSQAVRNEAKSRDLTVFDATCPLVTKVHMEVARASRRGEESILIG
HAGHPEVEGTMGQYSNPEGGMYLVESPDDVWKLTVKNEEKLSFMTQTTLSVDDTSDVIDA
LRKRFPKIVGPRKDDICYATTNRQEAVRALAEQAEVVLVVGSKNSSNSNRLAELAQRMGK
RAFLIDDAKDIQEEWVKEVKCVGVTAGASAPDILVQNVVARLQQLGGGEAIPLEGREENI
VFEVPKELRVDIREVD
References
External Links:
ResourceLink
Uniprot ID:P62623
Uniprot Name:ISPH_ECOLI
GenBank Gene ID:AP009048
Genebank Protein ID:21321911
Ecogene ID:EG11081
Ecocyc:EG11081
ColiBase:b0029
Kegg Gene:b0029
EchoBASE ID:EB1073
CCDB:ISPH_ECOLI
BacMap:16128023
General Reference:
  • Adam, P., Hecht, S., Eisenreich, W., Kaiser, J., Grawert, T., Arigoni, D., Bacher, A., Rohdich, F. (2002). "Biosynthesis of terpenes: studies on 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase." Proc Natl Acad Sci U S A 99:12108-12113. Pubmed: 12198182
  • Altincicek, B., Kollas, A., Eberl, M., Wiesner, J., Sanderbrand, S., Hintz, M., Beck, E., Jomaa, H. (2001). "LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli." FEBS Lett 499:37-40. Pubmed: 11418107
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Bouvier, J., Stragier, P. (1991). "Nucleotide sequence of the lsp-dapB interval in Escherichia coli." Nucleic Acids Res 19:180. Pubmed: 2011499
  • 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. (2004). "IspH protein of Escherichia coli: studies on iron-sulfur cluster implementation and catalysis." J Am Chem Soc 126:12847-12855. Pubmed: 15469281
  • Gustafson, C. E., Kaul, S., Ishiguro, E. E. (1993). "Identification of the Escherichia coli lytB gene, which is involved in penicillin tolerance and control of the stringent response." J Bacteriol 175:1203-1205. Pubmed: 8432714
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • McAteer, S., Coulson, A., McLennan, N., Masters, M. (2001). "The lytB gene of Escherichia coli is essential and specifies a product needed for isoprenoid biosynthesis." J Bacteriol 183:7403-7407. Pubmed: 11717301
  • Rohdich, F., Hecht, S., Gartner, K., Adam, P., Krieger, C., Amslinger, S., Arigoni, D., Bacher, A., Eisenreich, W. (2002). "Studies on the nonmevalonate terpene biosynthetic pathway: metabolic role of IspH (LytB) protein." Proc Natl Acad Sci U S A 99:1158-1163. Pubmed: 11818558
  • Rohdich, F., Zepeck, F., Adam, P., Hecht, S., Kaiser, J., Laupitz, R., Grawert, T., Amslinger, S., Eisenreich, W., Bacher, A., Arigoni, D. (2003). "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 100:1586-1591. Pubmed: 12571359
  • Wolff, M., Seemann, M., Tse Sum Bui, B., Frapart, Y., Tritsch, D., Garcia Estrabot, A., Rodriguez-Concepcion, M., Boronat, A., Marquet, A., Rohmer, M. (2003). "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 541:115-120. Pubmed: 12706830
  • Yura, T., Mori, H., Nagai, H., Nagata, T., Ishihama, A., Fujita, N., Isono, K., Mizobuchi, K., Nakata, A. (1992). "Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region." Nucleic Acids Res 20:3305-3308. Pubmed: 1630901