ISPH_AQUAE
ID ISPH_AQUAE Reviewed; 289 AA.
AC O67625;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=4-hydroxy-3-methylbut-2-enyl diphosphate reductase {ECO:0000255|HAMAP-Rule:MF_00191};
DE Short=HMBPP reductase {ECO:0000255|HAMAP-Rule:MF_00191};
DE EC=1.17.7.4 {ECO:0000255|HAMAP-Rule:MF_00191, ECO:0000269|PubMed:12482608};
GN Name=ispH {ECO:0000255|HAMAP-Rule:MF_00191}; Synonyms=lytB;
GN OrderedLocusNames=aq_1739;
OS Aquifex aeolicus (strain VF5).
OC Bacteria; Aquificae; Aquificales; Aquificaceae; Aquifex.
OX NCBI_TaxID=224324;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=VF5;
RX PubMed=9537320; DOI=10.1038/32831;
RA Deckert G., Warren P.V., Gaasterland T., Young W.G., Lenox A.L.,
RA Graham D.E., Overbeek R., Snead M.A., Keller M., Aujay M., Huber R.,
RA Feldman R.A., Short J.M., Olsen G.J., Swanson R.V.;
RT "The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.";
RL Nature 392:353-358(1998).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, PRESENCE OF AN IRON-SULFUR CLUSTER, ACTIVITY
RP REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12482608; DOI=10.1016/s0014-5793(02)03726-2;
RA Altincicek B., Duin E.C., Reichenberg A., Hedderich R., Kollas A.-K.,
RA Hintz M., Wagner S., Wiesner J., Beck E., Jomaa H.;
RT "LytB protein catalyzes the terminal step of the 2-C-methyl-D-erythritol-4-
RT phosphate pathway of isoprenoid biosynthesis.";
RL FEBS Lett. 532:437-440(2002).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR
RP (3FE-4S), AND COFACTOR.
RX PubMed=19035630; DOI=10.1021/ja806668q;
RA Rekittke I., Wiesner J., Roehrich R., Demmer U., Warkentin E., Xu W.,
RA Troschke K., Hintz M., No J.H., Duin E.C., Oldfield E., Jomaa H.,
RA Ermler U.;
RT "Structure of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, the
RT terminal enzyme of the non-mevalonate pathway.";
RL J. Am. Chem. Soc. 130:17206-17207(2008).
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 {ECO:0000255|HAMAP-Rule:MF_00191, ECO:0000269|PubMed:12482608}.
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:0000255|HAMAP-Rule:MF_00191,
CC ECO:0000269|PubMed:12482608};
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:0000255|HAMAP-Rule:MF_00191,
CC ECO:0000269|PubMed:12482608};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00191};
CC Note=Was shown to bind 1 [3Fe-4S] cluster per subunit
CC (PubMed:19035630). However, it likely initially contains a [4Fe-4S]
CC cluster which easily degrades into a [3Fe-4S] form in the presence of
CC oxygen (By similarity). {ECO:0000250|UniProtKB:P62623,
CC ECO:0000255|HAMAP-Rule:MF_00191, ECO:0000269|PubMed:19035630};
CC -!- ACTIVITY REGULATION: Highly sensitive to dioxygen.
CC {ECO:0000269|PubMed:12482608}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=590 uM for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate
CC {ECO:0000269|PubMed:12482608};
CC pH dependence:
CC Optimum pH is 7.0-7.5. {ECO:0000269|PubMed:12482608};
CC Temperature dependence:
CC Optimum temperature is 60 degrees Celsius.
CC {ECO:0000269|PubMed:12482608};
CC -!- PATHWAY: Isoprenoid biosynthesis; dimethylallyl diphosphate
CC biosynthesis; dimethylallyl diphosphate from (2E)-4-hydroxy-3-
CC methylbutenyl diphosphate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00191}.
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:0000255|HAMAP-Rule:MF_00191}.
CC -!- SIMILARITY: Belongs to the IspH family. {ECO:0000255|HAMAP-
CC Rule:MF_00191}.
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DR EMBL; AE000657; AAC07596.1; -; Genomic_DNA.
DR PIR; G70449; G70449.
DR RefSeq; NP_214191.1; NC_000918.1.
DR RefSeq; WP_010881128.1; NC_000918.1.
DR PDB; 3DNF; X-ray; 1.65 A; A/B=1-289.
DR PDBsum; 3DNF; -.
DR AlphaFoldDB; O67625; -.
DR SMR; O67625; -.
DR STRING; 224324.aq_1739; -.
DR BindingDB; O67625; -.
DR ChEMBL; CHEMBL2242741; -.
DR EnsemblBacteria; AAC07596; AAC07596; aq_1739.
DR KEGG; aae:aq_1739; -.
DR PATRIC; fig|224324.8.peg.1338; -.
DR eggNOG; COG0761; Bacteria.
DR HOGENOM; CLU_027486_0_1_0; -.
DR InParanoid; O67625; -.
DR OMA; HNKYVVD; -.
DR OrthoDB; 1235756at2; -.
DR BRENDA; 1.17.7.4; 396.
DR UniPathway; UPA00056; UER00097.
DR UniPathway; UPA00059; UER00105.
DR EvolutionaryTrace; O67625; -.
DR Proteomes; UP000000798; Chromosome.
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: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; IEA:UniProtKB-UniRule.
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..289
FT /note="4-hydroxy-3-methylbut-2-enyl diphosphate reductase"
FT /id="PRO_0000128766"
FT ACT_SITE 126
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 13
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191,
FT ECO:0000305|PubMed:19035630"
FT BINDING 42
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 74
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 96
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191,
FT ECO:0000305|PubMed:19035630"
FT BINDING 124
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 165
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 193
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191,
FT ECO:0000305|PubMed:19035630"
FT BINDING 221..223
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 265
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 14..26
FT /evidence="ECO:0007829|PDB:3DNF"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 44..53
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 78..86
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 97..111
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 125..136
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 141..146
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 147..155
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 169..182
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 183..189
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 195..206
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 210..217
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 222..234
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 236..243
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 249..252
FT /evidence="ECO:0007829|PDB:3DNF"
FT STRAND 256..262
FT /evidence="ECO:0007829|PDB:3DNF"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:3DNF"
SQ SEQUENCE 289 AA; 32104 MW; A9D910C41727E9F4 CRC64;
MVDIIIAEHA GFCFGVKRAV KLAEESLKES QGKVYTLGPI IHNPQEVNRL KNLGVFPSQG
EEFKEGDTVI IRSHGIPPEK EEALRKKGLK VIDATCPYVK AVHEAVCQLT REGYFVVLVG
EKNHPEVIGT LGYLRACNGK GIVVETLEDI GEALKHERVG IVAQTTQNEE FFKEVVGEIA
LWVKEVKVIN TICNATSLRQ ESVKKLAPEV DVMIIIGGKN SGNTRRLYYI SKELNPNTYH
IETAEELQPE WFRGVKRVGI SAGASTPDWI IEQVKSRIQE ICEGQLVSS
