ODP2_MYCTU
ID ODP2_MYCTU Reviewed; 553 AA.
AC P9WIS7; L0TBM6; P65633; Q10381;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex;
DE EC=2.3.1.12;
DE AltName: Full=Component of peroxynitrite reductase/peroxidase complex;
DE Short=Component of PNR/P;
DE AltName: Full=Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex;
DE AltName: Full=Pyruvate dehydrogenase complex component E2;
DE Short=PDH component E2;
GN Name=dlaT; Synonyms=sucB; OrderedLocusNames=Rv2215; ORFNames=MTCY190.26;
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, FUNCTION AS AN ANTIOXIDANT, LIPOYLATION AT LYS-43 AND
RP LYS-162, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11799204; DOI=10.1126/science.1067798;
RA Bryk R., Lima C.D., Erdjument-Bromage H., Tempst P., Nathan C.;
RT "Metabolic enzymes of mycobacteria linked to antioxidant defense by a
RT thioredoxin-like protein.";
RL Science 295:1073-1077(2002).
RN [3]
RP FUNCTION AS A PDH COMPONENT, PH DEPENDENCE, LIPOYLATION, DISRUPTION
RP PHENOTYPE, GENE NAME, AND IDENTIFICATION IN THE PDH COMPLEX.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16045627; DOI=10.1111/j.1365-2958.2005.04741.x;
RA Tian J., Bryk R., Shi S., Erdjument-Bromage H., Tempst P., Nathan C.;
RT "Mycobacterium tuberculosis appears to lack alpha-ketoglutarate
RT dehydrogenase and encodes pyruvate dehydrogenase in widely separated
RT genes.";
RL Mol. Microbiol. 57:859-868(2005).
RN [4]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16368957; DOI=10.1128/iai.74.1.56-63.2006;
RA Shi S., Ehrt S.;
RT "Dihydrolipoamide acyltransferase is critical for Mycobacterium
RT tuberculosis pathogenesis.";
RL Infect. Immun. 74:56-63(2006).
RN [5]
RP ROLE IN VIRULENCE, INHIBITORS, ACTIVITY REGULATION, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18329613; DOI=10.1016/j.chom.2008.02.003;
RA Bryk R., Gold B., Venugopal A., Singh J., Samy R., Pupek K., Cao H.,
RA Popescu C., Gurney M., Hotha S., Cherian J., Rhee K., Ly L., Converse P.J.,
RA Ehrt S., Vandal O., Jiang X., Schneider J., Lin G., Nathan C.;
RT "Selective killing of nonreplicating mycobacteria.";
RL Cell Host Microbe 3:137-145(2008).
RN [6]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21238944; DOI=10.1016/j.chom.2010.12.004;
RA Venugopal A., Bryk R., Shi S., Rhee K., Rath P., Schnappinger D., Ehrt S.,
RA Nathan C.;
RT "Virulence of Mycobacterium tuberculosis depends on lipoamide
RT dehydrogenase, a member of three multienzyme complexes.";
RL Cell Host Microbe 9:21-31(2011).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-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).
CC -!- FUNCTION: Component of the pyruvate dehydrogenase (PDH) complex, that
CC catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2).
CC -!- FUNCTION: Together with AhpC, AhpD and Lpd, constitutes an NADH-
CC dependent peroxidase active against hydrogen and alkyl peroxides as
CC well as serving as a peroxynitrite reductase, thus protecting the
CC bacterium against reactive nitrogen intermediates and oxidative stress
CC generated by the host immune system.
CC -!- FUNCTION: Appears to be essential for Mtb pathogenesis.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[protein] + acetyl-CoA = (R)-
CC N(6)-(S(8)-acetyldihydrolipoyl)-L-lysyl-[protein] + CoA;
CC Xref=Rhea:RHEA:17017, Rhea:RHEA-COMP:10475, Rhea:RHEA-COMP:10478,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:83100,
CC ChEBI:CHEBI:83111; EC=2.3.1.12;
CC -!- COFACTOR:
CC Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088;
CC Note=Binds 2 lipoyl cofactors covalently.;
CC -!- ACTIVITY REGULATION: Inhibited by rhodanine compounds. Some of them
CC almost exclusively kill non-replicating mycobacteria in synergy with
CC products of host immunity, such as nitric oxide and hypoxia, and are
CC effective on bacteria within macrophages.
CC {ECO:0000269|PubMed:18329613}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.0 for PDH complex activity. Half-maximal activity is
CC observed at pH 7.0 and pH 9.0. Activity is abolished at pH < 5.
CC {ECO:0000269|PubMed:16045627};
CC -!- SUBUNIT: Forms a 24-polypeptide structural core with octahedral
CC symmetry (By similarity). Identified in a complex with AhpC, AhpD and
CC Lpd. Part of the PDH complex, consisting of multiple copies of AceE
CC (E1), DlaT (E2) and Lpd (E3). {ECO:0000250,
CC ECO:0000269|PubMed:11799204, ECO:0000269|PubMed:16045627}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene show severely retarded
CC growth in vitro, and display no PDH activity. They are also more
CC sensitive to nitrosative stress caused by NaNO(2), and to macrophage-
CC induced killing in vitro. They also show at least 20-fold reduction in
CC survival in a mouse tuberculosis model, and are unable to cause disease
CC in a guinea pig model of tuberculosis infection. Disruption of dlaT
CC leads to high up-regulation of the expression of the bkdABC operon.
CC {ECO:0000269|PubMed:16045627, ECO:0000269|PubMed:16368957,
CC ECO:0000269|PubMed:18329613, ECO:0000269|PubMed:21238944}.
CC -!- MISCELLANEOUS: Is the only lipoylated protein in strain H37Rv grown on
CC a standard rich medium. However, in a DlaT-deficient strain, another
CC protein, BkdC, becomes lipoylated.
CC -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP44992.1; -; Genomic_DNA.
DR PIR; H70786; H70786.
DR RefSeq; NP_216731.1; NC_000962.3.
DR RefSeq; WP_003411450.1; NZ_NVQJ01000008.1.
DR AlphaFoldDB; P9WIS7; -.
DR SMR; P9WIS7; -.
DR STRING; 83332.Rv2215; -.
DR BindingDB; P9WIS7; -.
DR ChEMBL; CHEMBL3988584; -.
DR iPTMnet; P9WIS7; -.
DR PaxDb; P9WIS7; -.
DR DNASU; 888777; -.
DR GeneID; 888777; -.
DR KEGG; mtu:Rv2215; -.
DR TubercuList; Rv2215; -.
DR eggNOG; COG0508; Bacteria.
DR OMA; MKVPSPG; -.
DR PhylomeDB; P9WIS7; -.
DR Reactome; R-HSA-1222541; Cell redox homeostasis.
DR SABIO-RK; P9WIS7; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0045254; C:pyruvate dehydrogenase complex; IDA:MTBBASE.
DR GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
DR GO; GO:0004148; F:dihydrolipoyl dehydrogenase activity; IDA:MTBBASE.
DR GO; GO:0004742; F:dihydrolipoyllysine-residue acetyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004149; F:dihydrolipoyllysine-residue succinyltransferase activity; IBA:GO_Central.
DR GO; GO:0015036; F:disulfide oxidoreductase activity; TAS:Reactome.
DR GO; GO:0031405; F:lipoic acid binding; IDA:MTBBASE.
DR GO; GO:0045454; P:cell redox homeostasis; IDA:MTBBASE.
DR GO; GO:1990748; P:cellular detoxification; IDA:MTBBASE.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-KW.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 4.10.320.10; -; 1.
DR InterPro; IPR003016; 2-oxoA_DH_lipoyl-BS.
DR InterPro; IPR001078; 2-oxoacid_DH_actylTfrase.
DR InterPro; IPR014276; 2-oxoglutarate_DH_E2.
DR InterPro; IPR000089; Biotin_lipoyl.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR036625; E3-bd_dom_sf.
DR InterPro; IPR004167; PSBD.
DR InterPro; IPR011053; Single_hybrid_motif.
DR Pfam; PF00198; 2-oxoacid_dh; 1.
DR Pfam; PF00364; Biotin_lipoyl; 2.
DR Pfam; PF02817; E3_binding; 1.
DR SUPFAM; SSF47005; SSF47005; 1.
DR SUPFAM; SSF51230; SSF51230; 2.
DR TIGRFAMs; TIGR02927; SucB_Actino; 1.
DR PROSITE; PS50968; BIOTINYL_LIPOYL; 2.
DR PROSITE; PS00189; LIPOYL; 2.
DR PROSITE; PS51826; PSBD; 1.
PE 1: Evidence at protein level;
KW Acetylation; Acyltransferase; Antioxidant; Glycolysis; Lipoyl;
KW Reference proteome; Repeat; Transferase; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..553
FT /note="Dihydrolipoyllysine-residue acetyltransferase
FT component of pyruvate dehydrogenase complex"
FT /id="PRO_0000162266"
FT DOMAIN 2..77
FT /note="Lipoyl-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 121..196
FT /note="Lipoyl-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 243..280
FT /note="Peripheral subunit-binding (PSBD)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01170"
FT REGION 81..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..238
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..321
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 95..113
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..232
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 523
FT /evidence="ECO:0000250"
FT ACT_SITE 527
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 43
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT ECO:0000305|PubMed:11799204"
FT MOD_RES 162
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT ECO:0000305|PubMed:11799204"
SQ SEQUENCE 553 AA; 57088 MW; 54B6E70D23B804A7 CRC64;
MAFSVQMPAL GESVTEGTVT RWLKQEGDTV ELDEPLVEVS TDKVDTEIPS PAAGVLTKII
AQEDDTVEVG GELAVIGDAK DAGEAAAPAP EKVPAAQPES KPAPEPPPVQ PTSGAPAGGD
AKPVLMPELG ESVTEGTVIR WLKKIGDSVQ VDEPLVEVST DKVDTEIPSP VAGVLVSISA
DEDATVPVGG ELARIGVAAD IGAAPAPKPA PKPVPEPAPT PKAEPAPSPP AAQPAGAAEG
APYVTPLVRK LASENNIDLA GVTGTGVGGR IRKQDVLAAA EQKKRAKAPA PAAQAAAAPA
PKAPPAPAPA LAHLRGTTQK ASRIRQITAN KTRESLQATA QLTQTHEVDM TKIVGLRARA
KAAFAEREGV NLTFLPFFAK AVIDALKIHP NINASYNEDT KEITYYDAEH LGFAVDTEQG
LLSPVIHDAG DLSLAGLARA IADIAARARS GNLKPDELSG GTFTITNIGS QGALFDTPIL
VPPQAAMLGT GAIVKRPRVV VDASGNESIG VRSVCYLPLT YDHRLIDGAD AGRFLTTIKH
RLEEGAFEAD LGL
