ISPH_ECOLI
ID ISPH_ECOLI Reviewed; 316 AA.
AC P62623; P22565;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=4-hydroxy-3-methylbut-2-enyl diphosphate reductase {ECO:0000303|PubMed:12706830};
DE Short=HMBPP reductase {ECO:0000303|PubMed:12706830};
DE EC=1.17.7.4 {ECO:0000269|PubMed:12198182, ECO:0000269|PubMed:12571359, ECO:0000269|PubMed:12706830};
DE AltName: Full=1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase {ECO:0000303|PubMed:12198182};
GN Name=ispH {ECO:0000303|PubMed:11818558}; Synonyms=lytB, yaaE;
GN OrderedLocusNames=b0029, JW0027;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RX PubMed=11818558; DOI=10.1073/pnas.032658999;
RA Rohdich F., Hecht S., Gaertner K., Adam P., Krieger C., Amslinger S.,
RA Arigoni D., Bacher A., Eisenreich W.;
RT "Studies on the nonmevalonate terpene biosynthetic pathway: metabolic role
RT of IspH (LytB) protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:1158-1163(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=2011499; DOI=10.1093/nar/19.1.180;
RA Bouvier J., Stragier P.;
RT "Nucleotide sequence of the lsp-dapB interval in Escherichia coli.";
RL Nucleic Acids Res. 19:180-180(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=1630901; DOI=10.1093/nar/20.13.3305;
RA Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K.,
RA Mizobuchi K., Nakata A.;
RT "Systematic sequencing of the Escherichia coli genome: analysis of the 0-
RT 2.4 min region.";
RL Nucleic Acids Res. 20:3305-3308(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [6]
RP IDENTIFICATION.
RX PubMed=8432714; DOI=10.1128/jb.175.4.1203-1205.1993;
RA Gustafson C.E., Kaul S., Ishiguro E.E.;
RT "Identification of the Escherichia coli lytB gene, which is involved in
RT penicillin tolerance and control of the stringent response.";
RL J. Bacteriol. 175:1203-1205(1993).
RN [7]
RP FUNCTION, PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / ATCC 23716 / DSM 498 / CIP 110067 / IMG 1711;
RX PubMed=11418107; DOI=10.1016/s0014-5793(01)02516-9;
RA Altincicek B., Kollas A.-K., Eberl M., Wiesner J., Sanderbrand S.,
RA Hintz M., Beck E., Jomaa H.;
RT "LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of
RT isoprenoid biosynthesis in Escherichia coli.";
RL FEBS Lett. 499:37-40(2001).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=11717301; DOI=10.1128/jb.183.24.7403-7407.2001;
RA McAteer S., Coulson A., McLennan N., Masters M.;
RT "The lytB gene of Escherichia coli is essential and specifies a product
RT needed for isoprenoid biosynthesis.";
RL J. Bacteriol. 183:7403-7407(2001).
RN [9]
RP CATALYTIC ACTIVITY.
RX PubMed=12198182; DOI=10.1073/pnas.182412599;
RA Adam P., Hecht S., Eisenreich W., Kaiser J., Graewert T., Arigoni D.,
RA Bacher A., Rohdich F.;
RT "Biosynthesis of terpenes: studies on 1-hydroxy-2-methyl-2-(E)-butenyl 4-
RT diphosphate reductase.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:12108-12113(2002).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBUNIT.
RX PubMed=12706830; DOI=10.1016/s0014-5793(03)00317-x;
RA Wolff M., Seemann M., Tse Sum Bui B., Frapart Y., Tritsch D.,
RA Garcia Estrabot A., Rodriguez-Concepcion M., Boronat A., Marquet A.,
RA Rohmer M.;
RT "Isoprenoid biosynthesis via the methylerythritol phosphate pathway: the
RT (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB/IspH) from
RT Escherichia coli is a [4Fe-4S] protein.";
RL FEBS Lett. 541:115-120(2003).
RN [11]
RP CATALYTIC ACTIVITY.
RX PubMed=12571359; DOI=10.1073/pnas.0337742100;
RA Rohdich F., Zepeck F., Adam P., Hecht S., Kaiser J., Laupitz R.,
RA Graewert T., Amslinger S., Eisenreich W., Bacher A., Arigoni D.;
RT "The deoxyxylulose phosphate pathway of isoprenoid biosynthesis: studies on
RT the mechanisms of the reactions catalyzed by IspG and IspH protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1586-1591(2003).
RN [12]
RP PRESENCE OF A 3FE-4S IRON-SULFUR CLUSTER, ACTIVITY REGULATION, KINETIC
RP PARAMETERS, AND MUTAGENESIS OF CYS-12; CYS-96 AND CYS-197.
RX PubMed=15469281; DOI=10.1021/ja0471727;
RA Graewert T., Kaiser J., Zepeck F., Laupitz R., Hecht S., Amslinger S.,
RA Schramek N., Schleicher E., Weber S., Haslbeck M., Buchner J., Rieder C.,
RA Arigoni D., Bacher A., Eisenreich W., Rohdich F.;
RT "IspH protein of Escherichia coli: studies on iron-sulfur cluster
RT implementation and catalysis.";
RL J. Am. Chem. Soc. 126:12847-12855(2004).
RN [13]
RP ACTIVITY REGULATION, AND COFACTOR.
RX PubMed=22012762; DOI=10.1002/anie.201104562;
RA Ahrens-Botzong A., Janthawornpong K., Wolny J.A., Tambou E.N., Rohmer M.,
RA Krasutsky S., Poulter C.D., Schuenemann V., Seemann M.;
RT "Biosynthesis of isoprene units: Moessbauer spectroscopy of substrate and
RT inhibitor binding to the [4Fe-4S] cluster of the LytB/IspH enzyme.";
RL Angew. Chem. Int. Ed. 50:11976-11979(2011).
RN [14] {ECO:0007744|PDB:3F7T}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR
RP (3FE-4S), FUNCTION, COFACTOR, AND MUTAGENESIS OF HIS-41; HIS-74; VAL-99;
RP HIS-124; GLU-126; THR-167; SER-225 AND ASN-227.
RX PubMed=19569147; DOI=10.1002/anie.200900548;
RA Graewert T., Rohdich F., Span I., Bacher A., Eisenreich W., Eppinger J.,
RA Groll M.;
RT "Structure of active IspH enzyme from Escherichia coli provides mechanistic
RT insights into substrate reduction.";
RL Angew. Chem. Int. Ed. Engl. 48:5756-5759(2009).
RN [15] {ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3KE9, ECO:0007744|PDB:3KEF, ECO:0007744|PDB:3KEL, ECO:0007744|PDB:3KEM}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE;
RP PRODUCTS; IRON-SULFUR (3FE-4S) AND IRON-SULFUR (4FE-4S), COFACTOR, AND
RP MUTAGENESIS OF CYS-12; CYS-96 AND CYS-197.
RC STRAIN=K12;
RX PubMed=20080550; DOI=10.1073/pnas.0913045107;
RA Graewert T., Span I., Eisenreich W., Rohdich F., Eppinger J., Bacher A.,
RA Groll M.;
RT "Probing the reaction mechanism of IspH protein by x-ray structure
RT analysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:1077-1081(2010).
RN [16] {ECO:0007744|PDB:4EB3}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-315 IN COMPLEX WITH ISO-HMBPP
RP AND IRON-SULFUR (4FE-4S), COFACTOR, REACTION MECHANISM, AND ACTIVE SITE.
RX PubMed=22687151; DOI=10.1021/ja303445z;
RA Wang W., Wang K., Span I., Jauch J., Bacher A., Groll M., Oldfield E.;
RT "Are free radicals involved in IspH catalysis? An EPR and crystallographic
RT investigation.";
RL J. Am. Chem. Soc. 134:11225-11234(2012).
RN [17] {ECO:0007744|PDB:3SZL, ECO:0007744|PDB:3SZO, ECO:0007744|PDB:3SZU, ECO:0007744|PDB:3T0F, ECO:0007744|PDB:3T0G}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF WILD-TYPE AND MUTANTS CYS-167;
RP ASP-126 AND GLN-126 IN COMPLEXES WITH SUBSTRATE AND IRON-SULFUR (4FE-4S),
RP FUNCTION, COFACTOR, MUTAGENESIS OF GLU-126 AND THR-167, REACTION MECHANISM,
RP AND ACTIVE SITE.
RX PubMed=22137895; DOI=10.1016/j.jmb.2011.11.033;
RA Span I., Graewert T., Bacher A., Eisenreich W., Groll M.;
RT "Crystal structures of mutant IspH proteins reveal a rotation of the
RT substrate's hydroxymethyl group during catalysis.";
RL J. Mol. Biol. 416:1-9(2012).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN COMPLEXES WITH VARIOUS COMPOUNDS;
RP IRON-SULFUR (3FE-4S) AND IRON-SULFUR (4FE-4S), FUNCTION, AND ACETYLENE
RP HYDRATASE ACTIVITY.
RX PubMed=22948824; DOI=10.1038/ncomms2052;
RA Span I., Wang K., Wang W., Zhang Y., Bacher A., Eisenreich W., Li K.,
RA Schulz C., Oldfield E., Groll M.;
RT "Discovery of acetylene hydratase activity of the iron-sulphur protein
RT IspH.";
RL Nat. Commun. 3:1042-1042(2012).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS
RP AND IRON-SULFUR (4FE-4S).
RA Borel F., Barbier E., Kratsutsky S., Janthawornpong K., Rohmer M.,
RA Dale Poulter C., Ferrer J.L., Seemann M.;
RT "Crystal structures of Escherichia coli Isph in complex with two potent
RT inhibitors of the methylerythritol phosphate pathway, a target for the
RT development of new antibacterial and antiparasitic drugs.";
RL Submitted (DEC-2012) to the PDB data bank.
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1-315 IN COMPLEXES WITH SUBSTRATE
RP ANALOGS AND IRON-SULFUR (4FE-4S).
RX PubMed=23307751; DOI=10.1002/anie.201208469;
RA Span I., Wang K., Wang W., Jauch J., Eisenreich W., Bacher A., Oldfield E.,
RA Groll M.;
RT "Structures of fluoro, amino, and thiol inhibitors bound to the [Fe4S4]
RT protein IspH.";
RL Angew. Chem. Int. Ed. Engl. 52:2118-2121(2013).
CC -!- FUNCTION: Catalyzes the conversion of 1-hydroxy-2-methyl-2-(E)-butenyl
CC 4-diphosphate (HMBPP) into a mixture of isopentenyl diphosphate (IPP)
CC and dimethylallyl diphosphate (DMAPP). Acts in the terminal step of the
CC DOXP/MEP pathway for isoprenoid precursor biosynthesis
CC (PubMed:11818558, PubMed:11418107, PubMed:12706830, PubMed:19569147,
CC PubMed:22137895). In vitro, can also hydrate acetylenes to aldehydes
CC and ketones via anti-Markovnikov/Markovnikov addition
CC (PubMed:22948824). {ECO:0000269|PubMed:11418107,
CC ECO:0000269|PubMed:11818558, ECO:0000269|PubMed:12706830,
CC ECO:0000269|PubMed:19569147, ECO:0000269|PubMed:22137895,
CC ECO:0000269|PubMed:22948824}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + isopentenyl diphosphate + 2 oxidized [2Fe-2S]-
CC [ferredoxin] = (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 H(+)
CC + 2 reduced [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:24488, Rhea:RHEA-
CC COMP:10000, Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:128753, ChEBI:CHEBI:128769; EC=1.17.7.4;
CC Evidence={ECO:0000269|PubMed:12198182, ECO:0000269|PubMed:12571359,
CC ECO:0000269|PubMed:12706830};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + H2O + 2 oxidized [2Fe-2S]-
CC [ferredoxin] = (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 H(+)
CC + 2 reduced [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:24825, Rhea:RHEA-
CC COMP:10000, Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:57623, ChEBI:CHEBI:128753; EC=1.17.7.4;
CC Evidence={ECO:0000269|PubMed:12198182, ECO:0000269|PubMed:12571359,
CC ECO:0000269|PubMed:12706830};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:12706830, ECO:0000269|PubMed:20080550,
CC ECO:0000269|PubMed:22012762, ECO:0000269|PubMed:22137895,
CC ECO:0000269|PubMed:22687151};
CC Note=Was shown to bind 1 [3Fe-4S] cluster per subunit (PubMed:19569147,
CC PubMed:20080550, PubMed:15469281). However, it initially contains a
CC [4Fe-4S] cluster which easily degrades into a [3Fe-4S] form in the
CC presence of oxygen (PubMed:12706830, PubMed:22137895, PubMed:20080550,
CC PubMed:22687151). {ECO:0000269|PubMed:12706830,
CC ECO:0000269|PubMed:15469281, ECO:0000269|PubMed:19569147,
CC ECO:0000269|PubMed:20080550, ECO:0000269|PubMed:22137895,
CC ECO:0000269|PubMed:22687151};
CC -!- ACTIVITY REGULATION: Addition of Ca(2+), Mg(2+), Mn(2+), Ni(2+), Co(2+)
CC or Fe(2+) decreases the catalytic activity (PubMed:15469281). Addition
CC of Zn(2+) results in complete loss of activity (PubMed:15469281). Is
CC potently inhibited by substrate analogs in which the hydroxy group in
CC HMBPP is replaced by an amino or thiol group (PubMed:22012762).
CC {ECO:0000269|PubMed:15469281, ECO:0000269|PubMed:22012762}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate
CC {ECO:0000269|PubMed:15469281};
CC pH dependence:
CC Optimum pH is 7.0.;
CC -!- PATHWAY: Isoprenoid biosynthesis; dimethylallyl diphosphate
CC biosynthesis; dimethylallyl diphosphate from (2E)-4-hydroxy-3-
CC methylbutenyl diphosphate: step 1/1. {ECO:0000269|PubMed:11818558,
CC ECO:0000305|PubMed:11418107}.
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via DXP pathway; isopentenyl diphosphate from 1-deoxy-D-xylulose 5-
CC phosphate: step 6/6. {ECO:0000269|PubMed:11818558,
CC ECO:0000305|PubMed:11418107}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12706830}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are viable only if the
CC medium is supplemented with mevalonate or the cells are complemented
CC with an episomal copy of ispH (PubMed:11418107). A conditional E.coli
CC lytB mutant shows that LytB is essential for survival and that
CC depletion of LytB results in cell lysis (PubMed:11717301).
CC {ECO:0000269|PubMed:11418107, ECO:0000269|PubMed:11717301}.
CC -!- SIMILARITY: Belongs to the IspH family. {ECO:0000255|HAMAP-
CC Rule:MF_00191}.
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DR EMBL; AY062212; AAL38655.1; -; Genomic_DNA.
DR EMBL; X54945; CAA38707.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73140.1; -; Genomic_DNA.
DR EMBL; AP009048; BAB96598.1; -; Genomic_DNA.
DR PIR; JE0403; JE0403.
DR RefSeq; NP_414570.1; NC_000913.3.
DR RefSeq; WP_001166395.1; NZ_SSZK01000004.1.
DR PDB; 3F7T; X-ray; 1.80 A; A/B=1-316.
DR PDB; 3KE8; X-ray; 1.70 A; A/B=1-316.
DR PDB; 3KE9; X-ray; 1.90 A; A/B=1-316.
DR PDB; 3KEF; X-ray; 1.70 A; A/B=1-316.
DR PDB; 3KEL; X-ray; 1.80 A; A/B=1-316.
DR PDB; 3KEM; X-ray; 2.00 A; A/B=1-316.
DR PDB; 3SZL; X-ray; 1.60 A; A/B=1-316.
DR PDB; 3SZO; X-ray; 1.60 A; A/B=1-316.
DR PDB; 3SZU; X-ray; 1.40 A; A/B=1-316.
DR PDB; 3T0F; X-ray; 1.90 A; A/B=1-316.
DR PDB; 3T0G; X-ray; 2.10 A; A/B=1-316.
DR PDB; 3URK; X-ray; 1.50 A; A/B=1-316.
DR PDB; 3UTC; X-ray; 1.90 A; A/B=1-316.
DR PDB; 3UTD; X-ray; 1.70 A; A/B=1-316.
DR PDB; 3UV3; X-ray; 1.60 A; A/B=1-316.
DR PDB; 3UV6; X-ray; 1.70 A; A/B=1-316.
DR PDB; 3UV7; X-ray; 1.60 A; A/B=1-316.
DR PDB; 3UWM; X-ray; 1.80 A; A/B=1-316.
DR PDB; 3ZGL; X-ray; 1.68 A; A/B=1-316.
DR PDB; 3ZGN; X-ray; 1.95 A; A/B=1-316.
DR PDB; 4EB3; X-ray; 1.90 A; A/B=1-315.
DR PDB; 4H4C; X-ray; 1.80 A; A/B=1-315.
DR PDB; 4H4D; X-ray; 1.35 A; A/B=1-315.
DR PDB; 4H4E; X-ray; 1.70 A; A/B=1-315.
DR PDBsum; 3F7T; -.
DR PDBsum; 3KE8; -.
DR PDBsum; 3KE9; -.
DR PDBsum; 3KEF; -.
DR PDBsum; 3KEL; -.
DR PDBsum; 3KEM; -.
DR PDBsum; 3SZL; -.
DR PDBsum; 3SZO; -.
DR PDBsum; 3SZU; -.
DR PDBsum; 3T0F; -.
DR PDBsum; 3T0G; -.
DR PDBsum; 3URK; -.
DR PDBsum; 3UTC; -.
DR PDBsum; 3UTD; -.
DR PDBsum; 3UV3; -.
DR PDBsum; 3UV6; -.
DR PDBsum; 3UV7; -.
DR PDBsum; 3UWM; -.
DR PDBsum; 3ZGL; -.
DR PDBsum; 3ZGN; -.
DR PDBsum; 4EB3; -.
DR PDBsum; 4H4C; -.
DR PDBsum; 4H4D; -.
DR PDBsum; 4H4E; -.
DR AlphaFoldDB; P62623; -.
DR SMR; P62623; -.
DR BioGRID; 4262917; 331.
DR BioGRID; 849179; 2.
DR DIP; DIP-35808N; -.
DR IntAct; P62623; 7.
DR STRING; 511145.b0029; -.
DR BindingDB; P62623; -.
DR DrugBank; DB01785; Dimethylallyl Diphosphate.
DR DrugBank; DB04714; ISOPENTENYL PYROPHOSPHATE.
DR jPOST; P62623; -.
DR PaxDb; P62623; -.
DR PRIDE; P62623; -.
DR EnsemblBacteria; AAC73140; AAC73140; b0029.
DR EnsemblBacteria; BAB96598; BAB96598; BAB96598.
DR GeneID; 58460832; -.
DR GeneID; 944777; -.
DR KEGG; ecj:JW0027; -.
DR KEGG; eco:b0029; -.
DR PATRIC; fig|1411691.4.peg.2256; -.
DR EchoBASE; EB1073; -.
DR eggNOG; COG0761; Bacteria.
DR HOGENOM; CLU_027486_1_0_6; -.
DR InParanoid; P62623; -.
DR OMA; HNKYVVD; -.
DR PhylomeDB; P62623; -.
DR BioCyc; EcoCyc:EG11081-MON; -.
DR BioCyc; MetaCyc:EG11081-MON; -.
DR UniPathway; UPA00056; UER00097.
DR UniPathway; UPA00059; UER00105.
DR EvolutionaryTrace; P62623; -.
DR PRO; PR:P62623; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0051538; F:3 iron, 4 sulfur cluster binding; IDA:EcoCyc.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule.
DR GO; GO:0051745; F:4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0042380; F:hydroxymethylbutenyl pyrophosphate reductase activity; IDA:EcoCyc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050992; P:dimethylallyl diphosphate biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0019288; P:isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway; IMP:EcoCyc.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniRule.
DR CDD; cd13944; lytB_ispH; 1.
DR HAMAP; MF_00191; IspH; 1.
DR InterPro; IPR003451; LytB/IspH.
DR PANTHER; PTHR30426; PTHR30426; 1.
DR Pfam; PF02401; LYTB; 1.
DR TIGRFAMs; TIGR00216; ispH_lytB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Iron; Iron-sulfur; Isoprene biosynthesis;
KW Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..316
FT /note="4-hydroxy-3-methylbut-2-enyl diphosphate reductase"
FT /id="PRO_0000128812"
FT ACT_SITE 126
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:22137895,
FT ECO:0000305|PubMed:22687151"
FT BINDING 12
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:20080550,
FT ECO:0000269|PubMed:22137895, ECO:0000269|PubMed:22687151,
FT ECO:0000269|PubMed:22948824, ECO:0000269|PubMed:23307751,
FT ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3SZL,
FT ECO:0007744|PDB:3URK, ECO:0007744|PDB:4EB3,
FT ECO:0007744|PDB:4H4C"
FT BINDING 41
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20080550,
FT ECO:0000269|PubMed:22137895, ECO:0000305|PubMed:22687151,
FT ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3SZL,
FT ECO:0007744|PDB:4EB3"
FT BINDING 74
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20080550,
FT ECO:0000269|PubMed:22137895, ECO:0000305|PubMed:22687151,
FT ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3SZL,
FT ECO:0007744|PDB:4EB3"
FT BINDING 96
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:20080550,
FT ECO:0000269|PubMed:22137895, ECO:0000269|PubMed:22687151,
FT ECO:0000269|PubMed:22948824, ECO:0000269|PubMed:23307751,
FT ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3SZL,
FT ECO:0007744|PDB:3URK, ECO:0007744|PDB:4EB3,
FT ECO:0007744|PDB:4H4C"
FT BINDING 124
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20080550,
FT ECO:0000269|PubMed:22137895, ECO:0000305|PubMed:22687151,
FT ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3SZL,
FT ECO:0007744|PDB:4EB3"
FT BINDING 167
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20080550,
FT ECO:0000269|PubMed:22137895, ECO:0000305|PubMed:22687151,
FT ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3SZL,
FT ECO:0007744|PDB:4EB3"
FT BINDING 197
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:20080550,
FT ECO:0000269|PubMed:22137895, ECO:0000269|PubMed:22687151,
FT ECO:0000269|PubMed:22948824, ECO:0000269|PubMed:23307751,
FT ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3SZL,
FT ECO:0007744|PDB:3URK, ECO:0007744|PDB:4EB3,
FT ECO:0007744|PDB:4H4C"
FT BINDING 225..227
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20080550,
FT ECO:0000269|PubMed:22137895, ECO:0000305|PubMed:22687151,
FT ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3SZL,
FT ECO:0007744|PDB:4EB3"
FT BINDING 269
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20080550,
FT ECO:0000269|PubMed:22137895, ECO:0000305|PubMed:22687151,
FT ECO:0007744|PDB:3KE8, ECO:0007744|PDB:3SZL,
FT ECO:0007744|PDB:4EB3"
FT MUTAGEN 12
FT /note="C->S: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:15469281,
FT ECO:0000269|PubMed:20080550"
FT MUTAGEN 41
FT /note="H->N: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:19569147"
FT MUTAGEN 74
FT /note="H->N: Reduces catalytic activity 2-fold."
FT /evidence="ECO:0000269|PubMed:19569147"
FT MUTAGEN 96
FT /note="C->S: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:15469281,
FT ECO:0000269|PubMed:20080550"
FT MUTAGEN 99
FT /note="V->A: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:19569147"
FT MUTAGEN 124
FT /note="H->N: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:19569147"
FT MUTAGEN 126
FT /note="E->D,Q: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:19569147,
FT ECO:0000269|PubMed:22137895"
FT MUTAGEN 167
FT /note="T->C: Reduces catalytic activity 3-fold."
FT /evidence="ECO:0000269|PubMed:19569147,
FT ECO:0000269|PubMed:22137895"
FT MUTAGEN 167
FT /note="T->S: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:19569147,
FT ECO:0000269|PubMed:22137895"
FT MUTAGEN 197
FT /note="C->S: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:15469281,
FT ECO:0000269|PubMed:20080550"
FT MUTAGEN 225
FT /note="S->C: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:19569147"
FT MUTAGEN 227
FT /note="N->Q: Reduces catalytic activity 20-fold."
FT /evidence="ECO:0000269|PubMed:19569147"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 13..29
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 43..51
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 54..59
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 78..86
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 97..112
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 125..131
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:3T0G"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 147..152
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 160..165
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:3T0F"
FT HELIX 171..184
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:3KEM"
FT HELIX 198..213
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 215..220
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 226..237
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 241..247
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:4H4D"
FT TURN 256..258
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 272..284
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:4H4D"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:4H4D"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:4H4D"
SQ SEQUENCE 316 AA; 34775 MW; 0E7B378BD49AB771 CRC64;
MQILLANPRG FCAGVDRAIS IVENALAIYG APIYVRHEVV HNRYVVDSLR ERGAIFIEQI
SEVPDGAILI FSAHGVSQAV RNEAKSRDLT VFDATCPLVT KVHMEVARAS RRGEESILIG
HAGHPEVEGT MGQYSNPEGG MYLVESPDDV WKLTVKNEEK LSFMTQTTLS VDDTSDVIDA
LRKRFPKIVG PRKDDICYAT TNRQEAVRAL AEQAEVVLVV GSKNSSNSNR LAELAQRMGK
RAFLIDDAKD IQEEWVKEVK CVGVTAGASA PDILVQNVVA RLQQLGGGEA IPLEGREENI
VFEVPKELRV DIREVD
