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P62623

- ISPH_ECOLI

UniProt

P62623 - ISPH_ECOLI

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Protein

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

Gene

ispH

Organism
Escherichia coli (strain K12)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

Isopentenyl diphosphate + NAD(P)+ + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H.
Dimethylallyl diphosphate + NAD(P)+ + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H.

Cofactori

Binds 1 3Fe-4S cluster per subunit.3 Publications

Enzyme regulationi

Addition of Ca2+, Mg2+, Mn2+, Ni2+, Co2+ or Fe2+ decreases the activity. Addition of Zn2+ results in complete loss of activity.1 Publication

Kineticsi

  1. KM=30 µM for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate1 Publication

pH dependencei

Optimum pH is 7.0.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi12 – 121Iron-sulfur (3Fe-4S)2 Publications
Binding sitei41 – 411Substrate2 Publications
Binding sitei74 – 741Substrate2 Publications
Metal bindingi96 – 961Iron-sulfur (3Fe-4S)2 Publications
Binding sitei124 – 1241Substrate2 Publications
Binding sitei167 – 1671Substrate2 Publications
Metal bindingi197 – 1971Iron-sulfur (3Fe-4S)2 Publications
Binding sitei269 – 2691Substrate2 Publications

GO - Molecular functioni

  1. 3 iron, 4 sulfur cluster binding Source: UniProtKB-HAMAP
  2. 4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase activity Source: UniProtKB-HAMAP
  3. hydroxymethylbutenyl pyrophosphate reductase activity Source: EcoCyc
  4. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. dimethylallyl diphosphate biosynthetic process Source: UniProtKB-UniPathway
  2. isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway Source: UniProtKB-HAMAP
  3. response to antibiotic Source: EcoCyc
  4. terpenoid biosynthetic process Source: UniProtKB-HAMAP
  5. ubiquinone biosynthetic process Source: EcoCyc
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Isoprene biosynthesis

Keywords - Ligandi

3Fe-4S, Iron, Iron-sulfur, Metal-binding, NADP

Enzyme and pathway databases

BioCyciEcoCyc:EG11081-MONOMER.
ECOL316407:JW0027-MONOMER.
MetaCyc:EG11081-MONOMER.
BRENDAi1.17.1.2. 2026.
UniPathwayiUPA00056; UER00097.
UPA00059; UER00105.

Names & Taxonomyi

Protein namesi
Recommended name:
4-hydroxy-3-methylbut-2-enyl diphosphate reductase (EC:1.17.1.2)
Gene namesi
Name:ispH
Synonyms:lytB, yaaE
Ordered Locus Names:b0029, JW0027
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
ProteomesiUP000000318: Chromosome, UP000000625: Chromosome

Organism-specific databases

EcoGeneiEG11081. ispH.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi12 – 121C → S: Loss of activity. 2 Publications
Mutagenesisi41 – 411H → N: No effect on the activity. 1 Publication
Mutagenesisi74 – 741H → N: Reduces activity 2-fold. 1 Publication
Mutagenesisi96 – 961C → S: Loss of activity. 2 Publications
Mutagenesisi99 – 991V → A: No effect on the activity. 1 Publication
Mutagenesisi124 – 1241H → N: Reduces activity 100-fold. 1 Publication
Mutagenesisi126 – 1261E → D or Q: Reduces activity 100-fold. 2 Publications
Mutagenesisi167 – 1671T → C: Reduces activity 3-fold. 2 Publications
Mutagenesisi167 – 1671T → S: No effect on the activity. 2 Publications
Mutagenesisi197 – 1971C → S: Loss of activity. 2 Publications
Mutagenesisi225 – 2251S → C: Reduces activity 100-fold. 1 Publication
Mutagenesisi227 – 2271N → Q: Reduces activity 20-fold. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 3163164-hydroxy-3-methylbut-2-enyl diphosphate reductasePRO_0000128812Add
BLAST

Proteomic databases

PaxDbiP62623.
PRIDEiP62623.

Expressioni

Gene expression databases

GenevestigatoriP62623.

Interactioni

Subunit structurei

Homodimer.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
dnaKP0A6Y81EBI-554022,EBI-542092

Protein-protein interaction databases

DIPiDIP-35808N.
IntActiP62623. 7 interactions.
STRINGi511145.b0029.

Structurei

Secondary structure

1
316
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi2 – 54Combined sources
Helixi13 – 2917Combined sources
Beta strandi33 – 375Combined sources
Beta strandi39 – 413Combined sources
Helixi43 – 519Combined sources
Beta strandi54 – 596Combined sources
Helixi60 – 623Combined sources
Beta strandi68 – 714Combined sources
Helixi78 – 869Combined sources
Beta strandi90 – 934Combined sources
Helixi97 – 11216Combined sources
Beta strandi115 – 1206Combined sources
Helixi125 – 1317Combined sources
Beta strandi137 – 1393Combined sources
Beta strandi141 – 1444Combined sources
Helixi147 – 1526Combined sources
Beta strandi160 – 1656Combined sources
Beta strandi167 – 1693Combined sources
Helixi171 – 18414Combined sources
Beta strandi191 – 1933Combined sources
Helixi198 – 21316Combined sources
Beta strandi215 – 2206Combined sources
Helixi226 – 23712Combined sources
Beta strandi241 – 2477Combined sources
Helixi248 – 2503Combined sources
Helixi253 – 2553Combined sources
Turni256 – 2583Combined sources
Beta strandi260 – 2667Combined sources
Helixi272 – 28413Combined sources
Beta strandi289 – 2924Combined sources
Beta strandi300 – 3023Combined sources
Helixi306 – 3083Combined sources

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3F7TX-ray1.80A/B1-316[»]
3KE8X-ray1.70A/B1-316[»]
3KE9X-ray1.90A/B1-316[»]
3KEFX-ray1.70A/B1-316[»]
3KELX-ray1.80A/B1-316[»]
3KEMX-ray2.00A/B1-316[»]
3SZLX-ray1.60A/B1-316[»]
3SZOX-ray1.60A/B1-316[»]
3SZUX-ray1.40A/B1-316[»]
3T0FX-ray1.90A/B1-316[»]
3T0GX-ray2.10A/B1-316[»]
3URKX-ray1.50A/B1-316[»]
3UTCX-ray1.90A/B1-316[»]
3UTDX-ray1.70A/B1-316[»]
3UV3X-ray1.60A/B1-316[»]
3UV6X-ray1.70A/B1-316[»]
3UV7X-ray1.60A/B1-316[»]
3UWMX-ray1.80A/B1-316[»]
3ZGLX-ray1.68A/B1-316[»]
3ZGNX-ray1.95A/B1-316[»]
4EB3X-ray1.90A/B1-315[»]
4H4CX-ray1.80A/B1-315[»]
4H4DX-ray1.35A/B1-315[»]
4H4EX-ray1.70A/B1-315[»]
ProteinModelPortaliP62623.
SMRiP62623. Positions 1-310.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62623.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni225 – 2273Substrate binding

Sequence similaritiesi

Belongs to the IspH family.Curated

Phylogenomic databases

eggNOGiCOG0761.
HOGENOMiHOG000220192.
InParanoidiP62623.
KOiK03527.
OMAiLEMYGAP.
OrthoDBiEOG6HF624.
PhylomeDBiP62623.

Family and domain databases

HAMAPiMF_00191. IspH.
InterProiIPR003451. LytB/IspH.
[Graphical view]
PfamiPF02401. LYTB. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00216. ispH_lytB. 1 hit.

Sequencei

Sequence statusi: Complete.

P62623-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MQILLANPRG FCAGVDRAIS IVENALAIYG APIYVRHEVV HNRYVVDSLR
60 70 80 90 100
ERGAIFIEQI SEVPDGAILI FSAHGVSQAV RNEAKSRDLT VFDATCPLVT
110 120 130 140 150
KVHMEVARAS RRGEESILIG HAGHPEVEGT MGQYSNPEGG MYLVESPDDV
160 170 180 190 200
WKLTVKNEEK LSFMTQTTLS VDDTSDVIDA LRKRFPKIVG PRKDDICYAT
210 220 230 240 250
TNRQEAVRAL AEQAEVVLVV GSKNSSNSNR LAELAQRMGK RAFLIDDAKD
260 270 280 290 300
IQEEWVKEVK CVGVTAGASA PDILVQNVVA RLQQLGGGEA IPLEGREENI
310
VFEVPKELRV DIREVD
Length:316
Mass (Da):34,775
Last modified:July 19, 2004 - v1
Checksum:i0E7B378BD49AB771
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY062212 Genomic DNA. Translation: AAL38655.1.
X54945 Genomic DNA. Translation: CAA38707.1.
U00096 Genomic DNA. Translation: AAC73140.1.
AP009048 Genomic DNA. Translation: BAB96598.1.
PIRiJE0403.
RefSeqiNP_414570.1. NC_000913.3.
YP_488335.1. NC_007779.1.

Genome annotation databases

EnsemblBacteriaiAAC73140; AAC73140; b0029.
BAB96598; BAB96598; BAB96598.
GeneIDi12933923.
944777.
KEGGiecj:Y75_p0029.
eco:b0029.
PATRICi32115149. VBIEscCol129921_0026.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY062212 Genomic DNA. Translation: AAL38655.1 .
X54945 Genomic DNA. Translation: CAA38707.1 .
U00096 Genomic DNA. Translation: AAC73140.1 .
AP009048 Genomic DNA. Translation: BAB96598.1 .
PIRi JE0403.
RefSeqi NP_414570.1. NC_000913.3.
YP_488335.1. NC_007779.1.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3F7T X-ray 1.80 A/B 1-316 [» ]
3KE8 X-ray 1.70 A/B 1-316 [» ]
3KE9 X-ray 1.90 A/B 1-316 [» ]
3KEF X-ray 1.70 A/B 1-316 [» ]
3KEL X-ray 1.80 A/B 1-316 [» ]
3KEM X-ray 2.00 A/B 1-316 [» ]
3SZL X-ray 1.60 A/B 1-316 [» ]
3SZO X-ray 1.60 A/B 1-316 [» ]
3SZU X-ray 1.40 A/B 1-316 [» ]
3T0F X-ray 1.90 A/B 1-316 [» ]
3T0G X-ray 2.10 A/B 1-316 [» ]
3URK X-ray 1.50 A/B 1-316 [» ]
3UTC X-ray 1.90 A/B 1-316 [» ]
3UTD X-ray 1.70 A/B 1-316 [» ]
3UV3 X-ray 1.60 A/B 1-316 [» ]
3UV6 X-ray 1.70 A/B 1-316 [» ]
3UV7 X-ray 1.60 A/B 1-316 [» ]
3UWM X-ray 1.80 A/B 1-316 [» ]
3ZGL X-ray 1.68 A/B 1-316 [» ]
3ZGN X-ray 1.95 A/B 1-316 [» ]
4EB3 X-ray 1.90 A/B 1-315 [» ]
4H4C X-ray 1.80 A/B 1-315 [» ]
4H4D X-ray 1.35 A/B 1-315 [» ]
4H4E X-ray 1.70 A/B 1-315 [» ]
ProteinModelPortali P62623.
SMRi P62623. Positions 1-310.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-35808N.
IntActi P62623. 7 interactions.
STRINGi 511145.b0029.

Proteomic databases

PaxDbi P62623.
PRIDEi P62623.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

EnsemblBacteriai AAC73140 ; AAC73140 ; b0029 .
BAB96598 ; BAB96598 ; BAB96598 .
GeneIDi 12933923.
944777.
KEGGi ecj:Y75_p0029.
eco:b0029.
PATRICi 32115149. VBIEscCol129921_0026.

Organism-specific databases

EchoBASEi EB1073.
EcoGenei EG11081. ispH.

Phylogenomic databases

eggNOGi COG0761.
HOGENOMi HOG000220192.
InParanoidi P62623.
KOi K03527.
OMAi LEMYGAP.
OrthoDBi EOG6HF624.
PhylomeDBi P62623.

Enzyme and pathway databases

UniPathwayi UPA00056 ; UER00097 .
UPA00059 ; UER00105 .
BioCyci EcoCyc:EG11081-MONOMER.
ECOL316407:JW0027-MONOMER.
MetaCyc:EG11081-MONOMER.
BRENDAi 1.17.1.2. 2026.

Miscellaneous databases

EvolutionaryTracei P62623.
PROi P62623.

Gene expression databases

Genevestigatori P62623.

Family and domain databases

HAMAPi MF_00191. IspH.
InterProi IPR003451. LytB/IspH.
[Graphical view ]
Pfami PF02401. LYTB. 1 hit.
[Graphical view ]
TIGRFAMsi TIGR00216. ispH_lytB. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Studies on the nonmevalonate terpene biosynthetic pathway: metabolic role of IspH (LytB) protein."
    Rohdich F., Hecht S., Gaertner K., Adam P., Krieger C., Amslinger S., Arigoni D., Bacher A., Eisenreich W.
    Proc. Natl. Acad. Sci. U.S.A. 99:1158-1163(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION.
  2. "Nucleotide sequence of the lsp-dapB interval in Escherichia coli."
    Bouvier J., Stragier P.
    Nucleic Acids Res. 19:180-180(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12.
  3. "Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region."
    Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K., Mizobuchi K., Nakata A.
    Nucleic Acids Res. 20:3305-3308(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  5. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
    Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
    Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  6. "Identification of the Escherichia coli lytB gene, which is involved in penicillin tolerance and control of the stringent response."
    Gustafson C.E., Kaul S., Ishiguro E.E.
    J. Bacteriol. 175:1203-1205(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION.
  7. "LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli."
    Altincicek B., Kollas A.-K., Eberl M., Wiesner J., Sanderbrand S., Hintz M., Beck E., Jomaa H.
    FEBS Lett. 499:37-40(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PATHWAY.
    Strain: K12 / ATCC 23716 / DSM 498.
  8. "The lytB gene of Escherichia coli is essential and specifies a product needed for isoprenoid biosynthesis."
    McAteer S., Coulson A., McLennan N., Masters M.
    J. Bacteriol. 183:7403-7407(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PATHWAY.
  9. "Biosynthesis of terpenes: studies on 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase."
    Adam P., Hecht S., Eisenreich W., Kaiser J., Graewert T., Arigoni D., Bacher A., Rohdich F.
    Proc. Natl. Acad. Sci. U.S.A. 99:12108-12113(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY.
  10. "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."
    Wolff M., Seemann M., Tse Sum Bui B., Frapart Y., Tritsch D., Garcia Estrabot A., Rodriguez-Concepcion M., Boronat A., Marquet A., Rohmer M.
    FEBS Lett. 541:115-120(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: IRON-SULFUR CLUSTER, SUBUNIT.
  11. "The deoxyxylulose phosphate pathway of isoprenoid biosynthesis: studies on the mechanisms of the reactions catalyzed by IspG and IspH protein."
    Rohdich F., Zepeck F., Adam P., Hecht S., Kaiser J., Laupitz R., Graewert T., Amslinger S., Eisenreich W., Bacher A., Arigoni D.
    Proc. Natl. Acad. Sci. U.S.A. 100:1586-1591(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY.
  12. Cited for: PRESENCE OF A 3FE-4S IRON-SULFUR CLUSTER, ENZYME REGULATION, KINETIC PARAMETERS, MUTAGENESIS OF CYS-12; CYS-96 AND CYS-197.
  13. "Structure of active IspH enzyme from Escherichia coli provides mechanistic insights into substrate reduction."
    Graewert T., Rohdich F., Span I., Bacher A., Eisenreich W., Eppinger J., Groll M.
    Angew. Chem. Int. Ed. Engl. 48:5756-5759(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR (3FE-4S), FUNCTION, COFACTOR, SUBUNIT, MUTAGENESIS OF HIS-41; HIS-74; VAL-99; HIS-124; GLU-126; THR-167; SER-225 AND ASN-227.
  14. "Probing the reaction mechanism of IspH protein by x-ray structure analysis."
    Graewert T., Span I., Eisenreich W., Rohdich F., Eppinger J., Bacher A., Groll M.
    Proc. Natl. Acad. Sci. U.S.A. 107:1077-1081(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND IRON-SULFUR (3FE-4S), FUNCTION, COFACTOR, SUBUNIT, MUTAGENESIS OF CYS-12; CYS-96 AND CYS-197.
  15. "Crystal structures of mutant IspH proteins reveal a rotation of the substrate's hydroxymethyl group during catalysis."
    Span I., Graewert T., Bacher A., Eisenreich W., Groll M.
    J. Mol. Biol. 416:1-9(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND IRON-SULFUR (4FE-4S), FUNCTION, COFACTOR, SUBUNIT, MUTAGENESIS OF GLU-126 AND THR-167.

Entry informationi

Entry nameiISPH_ECOLI
AccessioniPrimary (citable) accession number: P62623
Secondary accession number(s): P22565
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 19, 2004
Last modified: October 29, 2014
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

PubMed:12706830 and PubMed:22137895 authors have reported the presence of a 4Fe-4S iron-sulfur cluster. It could be due to experimental conditions.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3