ID ISPH_BUCAI Reviewed; 319 AA. AC P57247; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 1. DT 04-NOV-2026, entry version 120. 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}; GN Name=ispH {ECO:0000255|HAMAP-Rule:MF_00191}; Synonyms=lytB; GN OrderedLocusNames=BU147; OS Buchnera aphidicola subsp. Acyrthosiphon pisum (strain APS) (Acyrthosiphon OS pisum symbiotic bacterium). OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Enterobacterales; Erwiniaceae; Buchnera. OX NCBI_TaxID=107806; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=APS; RX PubMed=10993077; DOI=10.1038/35024074; RA Shigenobu S., Watanabe H., Hattori M., Sakaki Y., Ishikawa H.; RT "Genome sequence of the endocellular bacterial symbiont of aphids Buchnera RT sp. APS."; RL Nature 407:81-86(2000). 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}. CC -!- CATALYTIC ACTIVITY: CC Reaction=isopentenyl diphosphate + 2 oxidized [2Fe-2S]-[ferredoxin] + CC H2O = (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 reduced [2Fe- CC 2S]-[ferredoxin] + 2 H(+); 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 -!- CATALYTIC ACTIVITY: CC Reaction=dimethylallyl diphosphate + 2 oxidized [2Fe-2S]-[ferredoxin] + CC H2O = (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 reduced [2Fe- CC 2S]-[ferredoxin] + 2 H(+); 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 -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000255|HAMAP-Rule:MF_00191}; CC Note=Binds 1 [4Fe-4S] cluster per subunit. {ECO:0000255|HAMAP- CC Rule:MF_00191}; 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 -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00191}. CC -!- SIMILARITY: Belongs to the IspH family. {ECO:0000255|HAMAP- CC Rule:MF_00191}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BA000003; BAB12865.1; -; Genomic_DNA. DR RefSeq; WP_009874103.1; NC_002528.1. DR AlphaFoldDB; P57247; -. DR SMR; P57247; -. DR STRING; 563178.BUAP5A_145; -. DR EnsemblBacteria; BAB12865; BAB12865; BAB12865. DR KEGG; buc:BU147; -. DR PATRIC; fig|107806.10.peg.156; -. DR eggNOG; COG0761; Bacteria. DR HOGENOM; CLU_027486_1_1_6; -. DR OMA; AAHLVDW; -. DR UniPathway; UPA00056; UER00097. DR UniPathway; UPA00059; UER00105. DR Proteomes; UP000001806; 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-enyl diphosphate reductase activity; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:InterPro. DR GO; GO:0050992; P:dimethylallyl diphosphate biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0019288; P:isopentenyl diphosphate biosynthetic process, methylerythritol phosphate pathway; IEA:UniProtKB-UniRule. DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniRule. DR CDD; cd13944; lytB_ispH; 1. DR Gene3D; 3.40.50.11270; -; 1. DR Gene3D; 3.40.1010.20; 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, catalytic domain; 2. DR HAMAP; MF_00191; IspH; 1. DR InterPro; IPR003451; LytB/IspH. DR NCBIfam; NF002188; ispH; 1. DR NCBIfam; TIGR00216; ispH_lytB; 1. DR NCBIfam; NF002190; PRK01045.1-4; 1. DR PANTHER; PTHR30426; 4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE; 1. DR PANTHER; PTHR30426:SF0; 4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE; 1. DR Pfam; PF02401; LYTB; 1. PE 3: Inferred from homology; KW 4Fe-4S; Iron; Iron-sulfur; Isoprene biosynthesis; Metal-binding; KW Oxidoreductase; Reference proteome. FT CHAIN 1..319 FT /note="4-hydroxy-3-methylbut-2-enyl diphosphate reductase" FT /id="PRO_0000128789" FT ACT_SITE 126 FT /note="Proton donor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 12 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 41 FT /ligand="(2E)-4-hydroxy-3-methylbut-2-enyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128753" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 41 FT /ligand="dimethylallyl diphosphate" FT /ligand_id="ChEBI:CHEBI:57623" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 41 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 74 FT /ligand="(2E)-4-hydroxy-3-methylbut-2-enyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128753" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 74 FT /ligand="dimethylallyl diphosphate" FT /ligand_id="ChEBI:CHEBI:57623" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 74 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" 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 BINDING 124 FT /ligand="(2E)-4-hydroxy-3-methylbut-2-enyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128753" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 124 FT /ligand="dimethylallyl diphosphate" FT /ligand_id="ChEBI:CHEBI:57623" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 124 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 167 FT /ligand="(2E)-4-hydroxy-3-methylbut-2-enyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128753" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 197 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 225 FT /ligand="(2E)-4-hydroxy-3-methylbut-2-enyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128753" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 225 FT /ligand="dimethylallyl diphosphate" FT /ligand_id="ChEBI:CHEBI:57623" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 225 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 226 FT /ligand="(2E)-4-hydroxy-3-methylbut-2-enyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128753" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 226 FT /ligand="dimethylallyl diphosphate" FT /ligand_id="ChEBI:CHEBI:57623" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 226 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 227 FT /ligand="(2E)-4-hydroxy-3-methylbut-2-enyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128753" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 227 FT /ligand="dimethylallyl diphosphate" FT /ligand_id="ChEBI:CHEBI:57623" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 227 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 269 FT /ligand="(2E)-4-hydroxy-3-methylbut-2-enyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128753" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 269 FT /ligand="dimethylallyl diphosphate" FT /ligand_id="ChEBI:CHEBI:57623" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" FT BINDING 269 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191" SQ SEQUENCE 319 AA; 35741 MW; 69D8AFCC12DD09B8 CRC64; MNIILTNPRG FCAGVKRAIL IVENALKVYK KTIYIRHELV HNQYVINTLR QKGVVFVEKI EQIPDYSVVI FSAHGVSKKV VQEAVKKKLI ILDATCPLVE KVHIEVSKSS EKAIETILIG HRGHPEVEGT IGQYNNKNGK IYLVESIEDV HNLSVQNSKK LNFFTQTTLS ITNTKKIIAA LKNKFPEISG PNKEDICYAT TNRQIAVRQL SKIADIIFVI GSNNSSNSNR LAELGKETGT FTKLISSFLD IKKKWLKNVN YIGITAGASA PEILVTEVIQ YLRKIGAHKP IEMIGVREKK IFKIPKKLLN IKTILDENG //