DLDH_YEAST
ID DLDH_YEAST Reviewed; 499 AA.
AC P09624; D6VTL1;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Dihydrolipoyl dehydrogenase, mitochondrial;
DE EC=1.8.1.4;
DE AltName: Full=Dihydrolipoamide dehydrogenase;
DE AltName: Full=Glycine decarboxylase complex subunit L;
DE AltName: Full=Lipoamide dehydrogenase component of pyruvate dehydrogenase complex;
DE AltName: Full=Pyruvate dehydrogenase complex E3 component;
DE Flags: Precursor;
GN Name=LPD1; Synonyms=DHLP1; OrderedLocusNames=YFL018C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3279419; DOI=10.1073/pnas.85.6.1831;
RA Browning K.S., Uhlinger D.J., Reed L.J.;
RT "Nucleotide sequence for yeast dihydrolipoamide dehydrogenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:1831-1834(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3058861; DOI=10.1099/00221287-134-5-1131;
RA Ross J., Reid G.A., Dawes I.W.;
RT "The nucleotide sequence of the LPD1 gene encoding lipoamide dehydrogenase
RT in Saccharomyces cerevisiae: comparison between eukaryotic and prokaryotic
RT sequences for related enzymes and identification of potential upstream
RT control sites.";
RL J. Gen. Microbiol. 134:1131-1139(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7670463; DOI=10.1038/ng0795-261;
RA Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S.,
RA Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H.,
RA Eki T.;
RT "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces
RT cerevisiae.";
RL Nat. Genet. 10:261-268(1995).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204511 / S288c / AB972;
RA Barrell B.G., Churcher C., Rajandream M.A.;
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP IDENTIFICATION IN GLYCINE DECARBOXYLASE COMPLEX.
RX PubMed=7498764; DOI=10.1093/genetics/140.4.1213;
RA Sinclair D.A., Dawes I.W.;
RT "Genetics of the synthesis of serine from glycine and the utilization of
RT glycine as sole nitrogen source by Saccharomyces cerevisiae.";
RL Genetics 140:1213-1222(1995).
RN [7]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH FAD, ACTIVE SITE, AND
RP DISULFIDE BOND.
RX PubMed=9538259; DOI=10.1093/oxfordjournals.jbchem.a021989;
RA Toyoda T., Suzuki K., Sekiguchi T., Reed L.J., Takenaka A.;
RT "Crystal structure of eucaryotic E3, lipoamide dehydrogenase from yeast.";
RL J. Biochem. 123:668-674(1998).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH FAD AND NAD.
RA Adachi W., Suzuki K., Tsunoda M., Sekiguchi T., Reed L.J., Takenaka A.;
RT "Crystal structure of yeast lipoamide dehydrogenase complexed with NAD+.";
RL Submitted (FEB-2005) to the PDB data bank.
CC -!- FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid
CC dehydrogenase complexes. This includes the pyruvate dehydrogenase
CC complex, which catalyzes the overall conversion of pyruvate to acetyl-
CC CoA and CO(2). Acts also as component of the glycine cleavage system
CC (glycine decarboxylase complex), which catalyzes the degradation of
CC glycine.
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: LPD1 is a homodimer. Eukaryotic pyruvate dehydrogenase (PDH)
CC complexes are organized as a core consisting of the oligomeric
CC dihydrolipoamide acetyl-transferase (E2), around which are arranged
CC multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide
CC dehydrogenase (E3) and protein X (E3BP) bound by non-covalent bonds.
CC LPD1 is a component of the glycine decarboxylase complex (GDC), which
CC is composed of four proteins: P, T, L and H.
CC {ECO:0000269|PubMed:7498764, ECO:0000269|PubMed:9538259,
CC ECO:0000269|Ref.9}.
CC -!- INTERACTION:
CC P09624; P19262: KGD2; NbExp=4; IntAct=EBI-5940, EBI-12464;
CC P09624; P19955: YMR31; NbExp=5; IntAct=EBI-5940, EBI-16295;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC -!- MISCELLANEOUS: Present with 24600 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
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DR EMBL; J03645; AAA34565.1; -; mRNA.
DR EMBL; M20880; AAB63974.1; -; Genomic_DNA.
DR EMBL; D50617; BAA09220.1; -; Genomic_DNA.
DR EMBL; Z46255; CAA86354.1; -; Genomic_DNA.
DR EMBL; BK006940; DAA12421.1; -; Genomic_DNA.
DR PIR; A30151; A30151.
DR RefSeq; NP_116635.1; NM_001179948.1.
DR PDB; 1JEH; X-ray; 2.40 A; A/B=22-499.
DR PDB; 1V59; X-ray; 2.20 A; A/B=22-499.
DR PDBsum; 1JEH; -.
DR PDBsum; 1V59; -.
DR AlphaFoldDB; P09624; -.
DR SMR; P09624; -.
DR BioGRID; 31128; 459.
DR ComplexPortal; CPX-1268; Glycine decarboxylase multienzyme complex.
DR ComplexPortal; CPX-1293; Mitochondrial 2-oxoglutarate dehydrogenase complex.
DR ComplexPortal; CPX-3207; Mitochondrial pyruvate dehydrogenase complex.
DR DIP; DIP-41N; -.
DR IntAct; P09624; 59.
DR MINT; P09624; -.
DR STRING; 4932.YFL018C; -.
DR iPTMnet; P09624; -.
DR UCD-2DPAGE; P09624; -.
DR MaxQB; P09624; -.
DR PaxDb; P09624; -.
DR PRIDE; P09624; -.
DR EnsemblFungi; YFL018C_mRNA; YFL018C; YFL018C.
DR GeneID; 850527; -.
DR KEGG; sce:YFL018C; -.
DR SGD; S000001876; LPD1.
DR VEuPathDB; FungiDB:YFL018C; -.
DR eggNOG; KOG1335; Eukaryota.
DR GeneTree; ENSGT00550000074844; -.
DR HOGENOM; CLU_016755_0_1_1; -.
DR InParanoid; P09624; -.
DR OMA; DAKYGEW; -.
DR BioCyc; YEAST:YFL018C-MON; -.
DR Reactome; R-SCE-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-SCE-6783984; Glycine degradation.
DR Reactome; R-SCE-70268; Pyruvate metabolism.
DR Reactome; R-SCE-71064; Lysine catabolism.
DR Reactome; R-SCE-71403; Citric acid cycle (TCA cycle).
DR EvolutionaryTrace; P09624; -.
DR PRO; PR:P09624; -.
DR Proteomes; UP000002311; Chromosome VI.
DR RNAct; P09624; protein.
DR GO; GO:0005960; C:glycine cleavage complex; IMP:SGD.
DR GO; GO:0005947; C:mitochondrial alpha-ketoglutarate dehydrogenase complex; IPI:ComplexPortal.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:SGD.
DR GO; GO:0009353; C:mitochondrial oxoglutarate dehydrogenase complex; IDA:SGD.
DR GO; GO:0005967; C:mitochondrial pyruvate dehydrogenase complex; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:ComplexPortal.
DR GO; GO:0045252; C:oxoglutarate dehydrogenase complex; IBA:GO_Central.
DR GO; GO:0004148; F:dihydrolipoyl dehydrogenase activity; IDA:SGD.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0004375; F:glycine dehydrogenase (decarboxylating) activity; IMP:SGD.
DR GO; GO:0004591; F:oxoglutarate dehydrogenase (succinyl-transferring) activity; IMP:SGD.
DR GO; GO:0004738; F:pyruvate dehydrogenase activity; IMP:SGD.
DR GO; GO:0006103; P:2-oxoglutarate metabolic process; IDA:ComplexPortal.
DR GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; IC:ComplexPortal.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0006546; P:glycine catabolic process; IMP:SGD.
DR GO; GO:0042743; P:hydrogen peroxide metabolic process; IMP:SGD.
DR GO; GO:0006550; P:isoleucine catabolic process; IMP:SGD.
DR GO; GO:0006564; P:L-serine biosynthetic process; IMP:SGD.
DR GO; GO:0006552; P:leucine catabolic process; IMP:SGD.
DR GO; GO:0006090; P:pyruvate metabolic process; IMP:SGD.
DR GO; GO:0006574; P:valine catabolic process; IMP:SGD.
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 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; FAD; Flavoprotein; Mitochondrion; NAD;
KW Oxidoreductase; Redox-active center; Reference proteome; Transit peptide.
FT TRANSIT 1..21
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:3279419"
FT CHAIN 22..499
FT /note="Dihydrolipoyl dehydrogenase, mitochondrial"
FT /id="PRO_0000030301"
FT ACT_SITE 478
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:9538259"
FT BINDING 56..65
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9538259, ECO:0000269|Ref.9"
FT BINDING 74
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9538259, ECO:0000269|Ref.9"
FT BINDING 139
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9538259, ECO:0000269|Ref.9"
FT BINDING 174..176
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 211..218
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 234
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 268
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 305
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 346
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9538259, ECO:0000269|Ref.9"
FT BINDING 352..355
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:9538259, ECO:0000269|Ref.9"
FT DISULFID 65..70
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:9538259"
FT STRAND 23..32
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 36..47
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 52..62
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 63..68
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 70..88
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 105..129
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 133..150
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 153..156
FT /evidence="ECO:0007829|PDB:1JEH"
FT STRAND 163..172
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 214..225
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 235..243
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 245..257
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 265..274
FT /evidence="ECO:0007829|PDB:1V59"
FT TURN 275..278
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 279..286
FT /evidence="ECO:0007829|PDB:1V59"
FT TURN 287..290
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 291..302
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:1V59"
FT TURN 311..313
FT /evidence="ECO:0007829|PDB:1JEH"
FT TURN 315..319
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 354..370
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 377..379
FT /evidence="ECO:0007829|PDB:1JEH"
FT STRAND 382..384
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 386..394
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 397..402
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 407..413
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 414..416
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 418..422
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 429..435
FT /evidence="ECO:0007829|PDB:1V59"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:1V59"
FT STRAND 440..448
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 451..463
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 468..472
FT /evidence="ECO:0007829|PDB:1V59"
FT HELIX 483..493
FT /evidence="ECO:0007829|PDB:1V59"
SQ SEQUENCE 499 AA; 54010 MW; 986A370F2E079DBC CRC64;
MLRIRSLLNN KRAFSSTVRT LTINKSHDVV IIGGGPAGYV AAIKAAQLGF NTACVEKRGK
LGGTCLNVGC IPSKALLNNS HLFHQMHTEA QKRGIDVNGD IKINVANFQK AKDDAVKQLT
GGIELLFKKN KVTYYKGNGS FEDETKIRVT PVDGLEGTVK EDHILDVKNI IVATGSEVTP
FPGIEIDEEK IVSSTGALSL KEIPKRLTII GGGIIGLEMG SVYSRLGSKV TVVEFQPQIG
ASMDGEVAKA TQKFLKKQGL DFKLSTKVIS AKRNDDKNVV EIVVEDTKTN KQENLEAEVL
LVAVGRRPYI AGLGAEKIGL EVDKRGRLVI DDQFNSKFPH IKVVGDVTFG PMLAHKAEEE
GIAAVEMLKT GHGHVNYNNI PSVMYSHPEV AWVGKTEEQL KEAGIDYKIG KFPFAANSRA
KTNQDTEGFV KILIDSKTER ILGAHIIGPN AGEMIAEAGL ALEYGASAED VARVCHAHPT
LSEAFKEANM AAYDKAIHC
