DLDH_MYCTO
ID DLDH_MYCTO Reviewed; 464 AA.
AC P9WHH8; L0T3N4; O53747; P66004;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Dihydrolipoyl dehydrogenase;
DE Short=LPD;
DE EC=1.8.1.4;
DE AltName: Full=Component of peroxynitrite reductase/peroxidase complex;
DE Short=Component of PNR/P;
DE AltName: Full=Dihydrolipoamide dehydrogenase;
DE AltName: Full=E3 component of alpha-ketoacid dehydrogenase complexes;
GN Name=lpdC; Synonyms=lpd; OrderedLocusNames=MT0478;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
CC -!- FUNCTION: Lipoamide dehydrogenase is an essential component of the
CC alpha-ketoacid dehydrogenase complexes, namely the pyruvate
CC dehydrogenase (PDH) complex, the branched-chain alpha-ketoacid
CC dehydrogenase (BCKADH) complex, and likely also the 2-oxoglutarate
CC dehydrogenase (ODH) complex. Catalyzes the reoxidation of dihydrolipoyl
CC groups which are covalently attached to the lipoate acyltransferase
CC components (E2) of the complexes (By similarity). {ECO:0000250}.
CC -!- FUNCTION: Together with AhpC, AhpD and DlaT, 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. {ECO:0000250}.
CC -!- FUNCTION: Appears to be essential for Mtb pathogenesis. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[protein] + NAD(+) = (R)-N(6)-
CC lipoyl-L-lysyl-[protein] + H(+) + NADH; Xref=Rhea:RHEA:15045,
CC Rhea:RHEA-COMP:10474, Rhea:RHEA-COMP:10475, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:83099,
CC ChEBI:CHEBI:83100; EC=1.8.1.4;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC Note=Binds 1 FAD per subunit. {ECO:0000250};
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
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DR EMBL; AE000516; AAK44702.1; -; Genomic_DNA.
DR PIR; B70828; B70828.
DR RefSeq; WP_003402301.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WHH8; -.
DR SMR; P9WHH8; -.
DR BindingDB; P9WHH8; -.
DR PRIDE; P9WHH8; -.
DR EnsemblBacteria; AAK44702; AAK44702; MT0478.
DR GeneID; 45424424; -.
DR KEGG; mtc:MT0478; -.
DR PATRIC; fig|83331.31.peg.508; -.
DR HOGENOM; CLU_016755_0_2_11; -.
DR BRENDA; 1.8.1.4; 3445.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
DR GO; GO:0004148; F:dihydrolipoyl dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-KW.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR InterPro; IPR006258; Lipoamide_DH.
DR InterPro; IPR001100; Pyr_nuc-diS_OxRdtase.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR TIGRFAMs; TIGR01350; lipoamide_DH; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 3: Inferred from homology;
KW Antioxidant; Cytoplasm; Disulfide bond; FAD; Flavoprotein; Glycolysis; NAD;
KW Oxidoreductase; Redox-active center; Tricarboxylic acid cycle; Virulence.
FT CHAIN 1..464
FT /note="Dihydrolipoyl dehydrogenase"
FT /id="PRO_0000428184"
FT ACT_SITE 443
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 33..41
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 50
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT BINDING 113
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 178..182
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 266..269
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 309
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 317
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT DISULFID 41..46
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 464 AA; 49239 MW; DD93D95DC6F76B22 CRC64;
MTHYDVVVLG AGPGGYVAAI RAAQLGLSTA IVEPKYWGGV CLNVGCIPSK ALLRNAELVH
IFTKDAKAFG ISGEVTFDYG IAYDRSRKVA EGRVAGVHFL MKKNKITEIH GYGTFADANT
LLVDLNDGGT ESVTFDNAII ATGSSTRLVP GTSLSANVVT YEEQILSREL PKSIIIAGAG
AIGMEFGYVL KNYGVDVTIV EFLPRALPNE DADVSKEIEK QFKKLGVTIL TATKVESIAD
GGSQVTVTVT KDGVAQELKA EKVLQAIGFA PNVEGYGLDK AGVALTDRKA IGVDDYMRTN
VGHIYAIGDV NGLLQLAHVA EAQGVVAAET IAGAETLTLG DHRMLPRATF CQPNVASFGL
TEQQARNEGY DVVVAKFPFT ANAKAHGVGD PSGFVKLVAD AKHGELLGGH LVGHDVAELL
PELTLAQRWD LTASELARNV HTHPTMSEAL QECFHGLVGH MINF
