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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, lytB, yaaE, b0029, JW0027
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.2 Publications
Dimethylallyl diphosphate + NAD(P)+ + H2O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H.2 Publications

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)
Binding sitei41 – 411Substrate
Binding sitei74 – 741Substrate
Metal bindingi96 – 961Iron-sulfur (3Fe-4S)
Binding sitei124 – 1241Substrate
Binding sitei167 – 1671Substrate
Metal bindingi197 – 1971Iron-sulfur (3Fe-4S)
Binding sitei269 – 2691Substrate

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 reductaseUniRule annotation
PRO_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

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

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.

Miscellaneous databases

EvolutionaryTraceiP62623.

Family & Domainsi

Region

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

Sequence similaritiesi

Belongs to the IspH family.

Phylogenomic databases

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

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

P62623-1 [UniParc]FASTAAdd to Basket

« Hide

MQILLANPRG FCAGVDRAIS IVENALAIYG APIYVRHEVV HNRYVVDSLR    50
ERGAIFIEQI SEVPDGAILI FSAHGVSQAV RNEAKSRDLT VFDATCPLVT 100
KVHMEVARAS RRGEESILIG HAGHPEVEGT MGQYSNPEGG MYLVESPDDV 150
WKLTVKNEEK LSFMTQTTLS VDDTSDVIDA LRKRFPKIVG PRKDDICYAT 200
TNRQEAVRAL AEQAEVVLVV GSKNSSNSNR LAELAQRMGK RAFLIDDAKD 250
IQEEWVKEVK CVGVTAGASA PDILVQNVVA RLQQLGGGEA IPLEGREENI 300
VFEVPKELRV DIREVD 316
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.
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.
[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: May 14, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

1 Publication and 1 Publication 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

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