ILVD_MYCTU
ID ILVD_MYCTU Reviewed; 575 AA.
AC P9WKJ5; L0T5Y5; O07433; P65154;
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=Dihydroxy-acid dehydratase {ECO:0000255|HAMAP-Rule:MF_00012, ECO:0000303|PubMed:31315931};
DE Short=DAD {ECO:0000255|HAMAP-Rule:MF_00012, ECO:0000303|PubMed:31315931};
DE EC=4.2.1.9 {ECO:0000269|PubMed:31315931};
GN Name=ilvD {ECO:0000255|HAMAP-Rule:MF_00012}; OrderedLocusNames=Rv0189c;
GN ORFNames=MTCI28.28c;
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 DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12657046; DOI=10.1046/j.1365-2958.2003.03425.x;
RA Sassetti C.M., Boyd D.H., Rubin E.J.;
RT "Genes required for mycobacterial growth defined by high density
RT mutagenesis.";
RL Mol. Microbiol. 48:77-84(2003).
RN [3]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT PRO-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [4] {ECO:0007744|PDB:6OVT}
RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, REACTION
RP MECHANISM, ACTIVE SITE, SUBUNIT, MUTAGENESIS OF SER-491, PATHWAY, AND
RP CARBOXYLATION AT LYS-139.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=31315931; DOI=10.1074/jbc.ra119.009498;
RA Bashiri G., Grove T.L., Hegde S.S., Lagautriere T., Gerfen G.J., Almo S.C.,
RA Squire C.J., Blanchard J.S., Baker E.N.;
RT "The active site of the Mycobacterium tuberculosis branched-chain amino
RT acid biosynthesis enzyme dihydroxyacid dehydratase contains a 2Fe-2S
RT cluster.";
RL J. Biol. Chem. 294:13158-13170(2019).
CC -!- FUNCTION: Functions in the biosynthesis of branched-chain amino acids.
CC Catalyzes the dehydration of (2R,3R)-2,3-dihydroxy-3-methylpentanoate
CC (2,3-dihydroxy-3-methylvalerate) into 2-oxo-3-methylpentanoate (2-oxo-
CC 3-methylvalerate) and of (2R)-2,3-dihydroxy-3-methylbutanoate (2,3-
CC dihydroxyisovalerate) into 2-oxo-3-methylbutanoate (2-oxoisovalerate),
CC the penultimate precursor to L-isoleucine and L-valine, respectively.
CC Is specific for the (R) isomer of 2,3-dihydroxy-3-methylbutanoate, with
CC no catalytic activity against the (S) isomer.
CC {ECO:0000269|PubMed:31315931}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate
CC + H2O; Xref=Rhea:RHEA:24809, ChEBI:CHEBI:11851, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:49072; EC=4.2.1.9;
CC Evidence={ECO:0000269|PubMed:31315931};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24810;
CC Evidence={ECO:0000305|PubMed:31315931};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3R)-2,3-dihydroxy-3-methylpentanoate = (S)-3-methyl-2-
CC oxopentanoate + H2O; Xref=Rhea:RHEA:27694, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35146, ChEBI:CHEBI:49258; EC=4.2.1.9;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00012};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27695;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00012};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000269|PubMed:31315931};
CC Note=Binds 1 [2Fe-2S] cluster per subunit. This cluster acts as a Lewis
CC acid cofactor. {ECO:0000269|PubMed:31315931};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:31315931};
CC -!- ACTIVITY REGULATION: Is competitively inhibited by aspterric acid in
CC vitro, which is thus a potential new lead compound for the design of
CC novel anti-TB drugs. {ECO:0000269|PubMed:31315931}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2025 uM for (2R)-2,3-dihydroxy-3-methylbutanoate
CC {ECO:0000269|PubMed:31315931};
CC Note=kcat is 112 min(-1) with (2R)-2,3-dihydroxy-3-methylbutanoate as
CC substrate. {ECO:0000269|PubMed:31315931};
CC pH dependence:
CC Optimum pH is about 7.8. {ECO:0000269|PubMed:31315931};
CC -!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-
CC isoleucine from 2-oxobutanoate: step 3/4.
CC {ECO:0000305|PubMed:31315931}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from
CC pyruvate: step 3/4. {ECO:0000305|PubMed:31315931}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:31315931}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene display impaired growth.
CC {ECO:0000269|PubMed:12657046}.
CC -!- SIMILARITY: Belongs to the IlvD/Edd family. {ECO:0000255|HAMAP-
CC Rule:MF_00012}.
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DR EMBL; AL123456; CCP42916.1; -; Genomic_DNA.
DR PIR; H70906; H70906.
DR RefSeq; NP_214703.1; NC_000962.3.
DR RefSeq; WP_003900824.1; NZ_NVQJ01000001.1.
DR PDB; 6OVT; X-ray; 1.88 A; A/B/C/D=1-575.
DR PDBsum; 6OVT; -.
DR AlphaFoldDB; P9WKJ5; -.
DR SMR; P9WKJ5; -.
DR STRING; 83332.Rv0189c; -.
DR iPTMnet; P9WKJ5; -.
DR PaxDb; P9WKJ5; -.
DR DNASU; 886774; -.
DR GeneID; 886774; -.
DR KEGG; mtu:Rv0189c; -.
DR TubercuList; Rv0189c; -.
DR eggNOG; COG0129; Bacteria.
DR OMA; PFGRYVM; -.
DR PhylomeDB; P9WKJ5; -.
DR UniPathway; UPA00047; UER00057.
DR UniPathway; UPA00049; UER00061.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004160; F:dihydroxy-acid dehydratase activity; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0009082; P:branched-chain amino acid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0009099; P:valine biosynthetic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.50.30.80; -; 1.
DR HAMAP; MF_00012; IlvD; 1.
DR InterPro; IPR042096; Dihydro-acid_dehy_C.
DR InterPro; IPR004404; DihydroxyA_deHydtase.
DR InterPro; IPR000581; DiOHA_6PGluconate_deHydtase.
DR InterPro; IPR020558; DiOHA_6PGluconate_deHydtase_CS.
DR InterPro; IPR037237; IlvD/EDD_N.
DR Pfam; PF00920; ILVD_EDD; 1.
DR SUPFAM; SSF143975; SSF143975; 1.
DR TIGRFAMs; TIGR00110; ilvD; 1.
DR PROSITE; PS00886; ILVD_EDD_1; 1.
DR PROSITE; PS00887; ILVD_EDD_2; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; 3D-structure; Acetylation; Amino-acid biosynthesis;
KW Branched-chain amino acid biosynthesis; Iron; Iron-sulfur; Lyase;
KW Magnesium; Metal-binding; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..575
FT /note="Dihydroxy-acid dehydratase"
FT /id="PRO_0000103481"
FT ACT_SITE 491
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:31315931"
FT BINDING 64
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000269|PubMed:31315931,
FT ECO:0007744|PDB:6OVT"
FT BINDING 96
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31315931,
FT ECO:0007744|PDB:6OVT"
FT BINDING 137
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000269|PubMed:31315931,
FT ECO:0007744|PDB:6OVT"
FT BINDING 138
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31315931,
FT ECO:0007744|PDB:6OVT"
FT BINDING 139
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /note="via carbamate group"
FT /evidence="ECO:0000269|PubMed:31315931,
FT ECO:0007744|PDB:6OVT"
FT BINDING 214
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000269|PubMed:31315931,
FT ECO:0007744|PDB:6OVT"
FT BINDING 465
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:31315931,
FT ECO:0007744|PDB:6OVT"
FT MOD_RES 2
FT /note="N-acetylproline"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 139
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000269|PubMed:31315931,
FT ECO:0007744|PDB:6OVT"
FT MUTAGEN 491
FT /note="S->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:31315931"
FT TURN 19..21
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 22..25
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 31..38
FT /evidence="ECO:0007829|PDB:6OVT"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 63..67
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 68..81
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 96..99
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 103..107
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 108..126
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 140..151
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 181..191
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 197..206
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 210..213
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 219..229
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 246..263
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 268..271
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 274..287
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 292..303
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 310..318
FT /evidence="ECO:0007829|PDB:6OVT"
FT TURN 327..329
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 334..339
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 343..352
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 368..375
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 382..385
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 392..395
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 399..403
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 410..412
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 414..416
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 420..431
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 432..440
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 448..454
FT /evidence="ECO:0007829|PDB:6OVT"
FT TURN 457..461
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 467..475
FT /evidence="ECO:0007829|PDB:6OVT"
FT TURN 479..481
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 483..489
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 496..500
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 511..514
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 520..524
FT /evidence="ECO:0007829|PDB:6OVT"
FT TURN 525..528
FT /evidence="ECO:0007829|PDB:6OVT"
FT STRAND 529..532
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 536..540
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 557..564
FT /evidence="ECO:0007829|PDB:6OVT"
FT HELIX 568..570
FT /evidence="ECO:0007829|PDB:6OVT"
SQ SEQUENCE 575 AA; 59352 MW; 6ECC279BF886A0F1 CRC64;
MPQTTDEAAS VSTVADIKPR SRDVTDGLEK AAARGMLRAV GMDDEDFAKP QIGVASSWNE
ITPCNLSLDR LANAVKEGVF SAGGYPLEFG TISVSDGISM GHEGMHFSLV SREVIADSVE
VVMQAERLDG SVLLAGCDKS LPGMLMAAAR LDLAAVFLYA GSILPGRAKL SDGSERDVTI
IDAFEAVGAC SRGLMSRADV DAIERAICPG EGACGGMYTA NTMASAAEAL GMSLPGSAAP
PATDRRRDGF ARRSGQAVVE LLRRGITARD ILTKEAFENA IAVVMAFGGS TNAVLHLLAI
AHEANVALSL QDFSRIGSGV PHLADVKPFG RHVMSDVDHI GGVPVVMKAL LDAGLLHGDC
LTVTGHTMAE NLAAITPPDP DGKVLRALAN PIHPSGGITI LHGSLAPEGA VVKTAGFDSD
VFEGTARVFD GERAALDALE DGTITVGDAV VIRYEGPKGG PGMREMLAIT GAIKGAGLGK
DVLLLTDGRF SGGTTGLCVG HIAPEAVDGG PIALLRNGDR IRLDVAGRVL DVLADPAEFA
SRQQDFSPPP PRYTTGVLSK YVKLVSSAAV GAVCG
