ISPH2_MYCTU
ID ISPH2_MYCTU Reviewed; 335 AA.
AC P9WKG1; L0T8I1; O53458; P0A5I0;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=4-hydroxy-3-methylbut-2-enyl diphosphate reductase 2 {ECO:0000255|HAMAP-Rule:MF_00191, ECO:0000303|PubMed:23091471, ECO:0000303|PubMed:26309039};
DE Short=HDR 2 {ECO:0000303|PubMed:26309039};
DE Short=HMBPP reductase 2 {ECO:0000255|HAMAP-Rule:MF_00191};
DE EC=1.17.7.4 {ECO:0000255|HAMAP-Rule:MF_00191, ECO:0000305|PubMed:23091471};
GN Name=ispH2 {ECO:0000305};
GN Synonyms=lytB2 {ECO:0000303|PubMed:23091471, ECO:0000303|PubMed:26309039,
GN ECO:0000312|EMBL:CCP43863.1}; OrderedLocusNames=Rv1110; ORFNames=MTV017.63;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23091471; DOI=10.3389/fmicb.2012.00368;
RA Mann F.M., Xu M., Davenport E.K., Peters R.J.;
RT "Functional characterization and evolution of the isotuberculosinol operon
RT in Mycobacterium tuberculosis and related Mycobacteria.";
RL Front. Microbiol. 3:368-368(2012).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=26309039; DOI=10.1371/journal.pone.0135638;
RA Brown A.C., Kokoczka R., Parish T.;
RT "LytB1 and LytB2 of Mycobacterium tuberculosis are not genetically
RT redundant.";
RL PLoS ONE 10:E0135638-E0135638(2015).
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) (PubMed:23091471). Acts in the
CC terminal step of the DOXP/MEP pathway for isoprenoid precursor
CC biosynthesis. Has a higher activity compared with LytB2
CC (PubMed:23091471). Is essential for M.tuberculosis growth in vitro
CC (PubMed:26309039). {ECO:0000255|HAMAP-Rule:MF_00191,
CC ECO:0000269|PubMed:23091471, ECO:0000269|PubMed:26309039}.
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:0000305|PubMed:23091471};
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:0000305|PubMed:23091471};
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 -!- DISRUPTION PHENOTYPE: The lytB2 gene cannot be deleted, unless an
CC additional copy is provided elsewhere, demonstrating that this is the
CC essential homolog. lytB1 cannot complement for loss of function of
CC lytB2, but the sole LytB homolog of M.smegmatis is able to compensate
CC for loss of LytB2 in M.tuberculosis. {ECO:0000269|PubMed:26309039}.
CC -!- SIMILARITY: Belongs to the IspH family. {ECO:0000255|HAMAP-
CC Rule:MF_00191}.
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DR EMBL; AL123456; CCP43863.1; -; Genomic_DNA.
DR PIR; D70898; D70898.
DR RefSeq; WP_003405853.1; NZ_NVQJ01000021.1.
DR RefSeq; YP_177788.1; NC_000962.3.
DR AlphaFoldDB; P9WKG1; -.
DR SMR; P9WKG1; -.
DR STRING; 83332.Rv1110; -.
DR PaxDb; P9WKG1; -.
DR DNASU; 885830; -.
DR GeneID; 45425084; -.
DR GeneID; 885830; -.
DR KEGG; mtu:Rv1110; -.
DR TubercuList; Rv1110; -.
DR eggNOG; COG0761; Bacteria.
DR OMA; HNKYVVD; -.
DR PhylomeDB; P9WKG1; -.
DR UniPathway; UPA00056; UER00097.
DR UniPathway; UPA00059; UER00105.
DR Proteomes; UP000001584; 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 4Fe-4S; Iron; Iron-sulfur; Isoprene biosynthesis; Metal-binding;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..335
FT /note="4-hydroxy-3-methylbut-2-enyl diphosphate reductase
FT 2"
FT /id="PRO_0000128841"
FT ACT_SITE 151
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 37
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 66
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 121
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 149
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 219
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 247..249
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
FT BINDING 292
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00191"
SQ SEQUENCE 335 AA; 36297 MW; E6640BC3246BDDBB CRC64;
MVPTVDMGIP GASVSSRSVA DRPNRKRVLL AEPRGYCAGV DRAVETVERA LQKHGPPVYV
RHEIVHNRHV VDTLAKAGAV FVEETEQVPE GAIVVFSAHG VAPTVHVSAS ERNLQVIDAT
CPLVTKVHNE ARRFARDDYD ILLIGHEGHE EVVGTAGEAP DHVQLVDGVD AVDQVTVRDE
DKVVWLSQTT LSVDETMEIV GRLRRRFPKL QDPPSDDICY ATQNRQVAVK AMAPECELVI
VVGSRNSSNS VRLVEVALGA GARAAHLVDW ADDIDSAWLD GVTTVGVTSG ASVPEVLVRG
VLERLAECGY DIVQPVTTAN ETLVFALPRE LRSPR
