DLDH_CHATD
ID DLDH_CHATD Reviewed; 504 AA.
AC G0SB20;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Dihydrolipoamide dehydrogenase {ECO:0000303|PubMed:33567276};
DE EC=1.8.1.4 {ECO:0000305|PubMed:33567276};
DE AltName: Full=Lipoamide dehydrogenase component of pyruvate dehydrogenase complex;
DE AltName: Full=Pyruvate dehydrogenase complex E3 component {ECO:0000303|PubMed:33567276};
DE Flags: Precursor;
GN ORFNames=CTHT_0048590;
OS Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Chaetomium.
OX NCBI_TaxID=759272;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 1495 / CBS 144.50 / IMI 039719;
RX PubMed=21784248; DOI=10.1016/j.cell.2011.06.039;
RA Amlacher S., Sarges P., Flemming D., van Noort V., Kunze R., Devos D.P.,
RA Arumugam M., Bork P., Hurt E.;
RT "Insight into structure and assembly of the nuclear pore complex by
RT utilizing the genome of a eukaryotic thermophile.";
RL Cell 146:277-289(2011).
RN [2]
RP FUNCTION, AND SUBUNIT.
RX PubMed=33567276; DOI=10.1016/j.celrep.2021.108727;
RA Kyrilis F.L., Semchonok D.A., Skalidis I., Tueting C., Hamdi F.,
RA O'Reilly F.J., Rappsilber J., Kastritis P.L.;
RT "Integrative structure of a 10-megadalton eukaryotic pyruvate dehydrogenase
RT complex from native cell extracts.";
RL Cell Rep. 34:108727-108727(2021).
RN [3]
RP FUNCTION, AND SUBUNIT.
RX PubMed=34836937; DOI=10.1038/s41467-021-27287-4;
RA Tueting C., Kyrilis F.L., Mueller J., Sorokina M., Skalidis I., Hamdi F.,
RA Sadian Y., Kastritis P.L.;
RT "Cryo-EM snapshots of a native lysate provide structural insights into a
RT metabolon-embedded transacetylase reaction.";
RL Nat. Commun. 12:6933-6933(2021).
CC -!- FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid
CC dehydrogenase complexes (By similarity). This includes the pyruvate
CC dehydrogenase complex, which catalyzes the overall conversion of
CC pyruvate to acetyl-CoA and CO(2). Acts also as component of the glycine
CC cleavage system (glycine decarboxylase complex), which catalyzes the
CC degradation of glycine (By similarity). The 10-megadalton pyruvate
CC dehydrogenase complex contains multiple copies of three enzymatic
CC components: pyruvate dehydrogenase (E1), dihydrolipoamide
CC acetyltransferase (E2) and lipoamide dehydrogenase (E3) and catalyzes
CC the overall oxidative decarboxylation of pyruvate to form acetyl-CoA
CC and CO(2) (PubMed:33567276, PubMed:34836937). Within the complex,
CC pyruvate and thiamine pyrophosphate (TPP or vitamin B1) are bound by
CC pyruvate dehydrogenase E1 subunits alpha and beta and pyruvate is
CC decarboxylated leading to the 2-carbon hydrohyethyl bound to TPP. The
CC E2 component contains covalently-bound lipoyl cofactors and transfers
CC the hydroxyethyl group from TPP to an oxidized form of covalently bound
CC lipoamide, and the resulting acetyl group is then transferred to free
CC coenzyme A to form acetyl-CoA and reduced dihydrolipoamide-E2. Finally,
CC the flavoprotein dihydrolipoamide dehydrogenase (E3) re-oxidizes the
CC lipoyl group of dihydrolipoamide-E2 to form lipoamide-E2 and NADH. A
CC fourth subunit, E3BP, is responsible for tethering E3 in proximity to
CC the core, forming the entire metabolon (Probable).
CC {ECO:0000250|UniProtKB:P09622, ECO:0000269|PubMed:33567276,
CC ECO:0000269|PubMed:34836937, ECO:0000305|PubMed:33567276}.
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 Evidence={ECO:0000250|UniProtKB:P09622};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15046;
CC Evidence={ECO:0000250|UniProtKB:P09622};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P09622};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P09622};
CC -!- SUBUNIT: Eukaryotic pyruvate dehydrogenase (PDH) complexes are
CC organized as a core consisting of the oligomeric dihydrolipoamide
CC acetyl-transferase (E2), around which are arranged multiple copies of
CC pyruvate dehydrogenase (E1), dihydrolipoamide dehydrogenase (E3) and
CC protein X (E3BP) bound by non-covalent bonds (PubMed:33567276). The
CC Chaetomium thermophilum PDH complex contains 60 E2 units, 12 E3BP
CC units, about 20 E1 units, and 12 or more E3 units (PubMed:33567276).
CC The units are organized in 1 E2 60-mer, 4 E3BP trimers, about 20 E1
CC tetramers, and a maximum of 12 E3 dimers (PubMed:33567276). The E3BP
CC trimers are bound inside the icosahedral core with tetrahedral symmetry
CC (PubMed:33567276). {ECO:0000269|PubMed:33567276}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255}.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC {ECO:0000250|UniProtKB:P09624}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
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DR EMBL; GL988044; EGS19400.1; -; Genomic_DNA.
DR RefSeq; XP_006695222.1; XM_006695159.1.
DR STRING; 759272.G0SB20; -.
DR EnsemblFungi; EGS19400; EGS19400; CTHT_0048590.
DR GeneID; 18258897; -.
DR KEGG; cthr:CTHT_0048590; -.
DR eggNOG; KOG1335; Eukaryota.
DR HOGENOM; CLU_016755_0_1_1; -.
DR OrthoDB; 581771at2759; -.
DR Proteomes; UP000008066; Unassembled WGS sequence.
DR GO; GO:0005960; C:glycine cleavage complex; IEA:EnsemblFungi.
DR GO; GO:0042645; C:mitochondrial nucleoid; IEA:EnsemblFungi.
DR GO; GO:0009353; C:mitochondrial oxoglutarate dehydrogenase complex; IEA:EnsemblFungi.
DR GO; GO:0005967; C:mitochondrial pyruvate dehydrogenase complex; IEA:EnsemblFungi.
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:0004375; F:glycine dehydrogenase (decarboxylating) activity; IEA:EnsemblFungi.
DR GO; GO:0004591; F:oxoglutarate dehydrogenase (succinyl-transferring) activity; IEA:EnsemblFungi.
DR GO; GO:0004738; F:pyruvate dehydrogenase activity; IEA:EnsemblFungi.
DR GO; GO:0006103; P:2-oxoglutarate metabolic process; IEA:EnsemblFungi.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0006546; P:glycine catabolic process; IEA:EnsemblFungi.
DR GO; GO:0042743; P:hydrogen peroxide metabolic process; IEA:EnsemblFungi.
DR GO; GO:0006550; P:isoleucine catabolic process; IEA:EnsemblFungi.
DR GO; GO:0006564; P:L-serine biosynthetic process; IEA:EnsemblFungi.
DR GO; GO:0006552; P:leucine catabolic process; IEA:EnsemblFungi.
DR GO; GO:0006090; P:pyruvate metabolic process; IEA:EnsemblFungi.
DR GO; GO:0006574; P:valine catabolic process; IEA:EnsemblFungi.
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 Disulfide bond; FAD; Flavoprotein; Mitochondrion; NAD; Nucleotide-binding;
KW Oxidoreductase; Redox-active center; Reference proteome; Transit peptide.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 35..504
FT /note="Dihydrolipoamide dehydrogenase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000456224"
FT ACT_SITE 483
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P09624"
FT BINDING 69..78
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09624"
FT BINDING 87
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09624"
FT BINDING 151
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09624"
FT BINDING 180..182
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 217..224
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 240
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 275
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 310
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT BINDING 351
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09624"
FT BINDING 357..360
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P09624"
FT SITE 444
FT /note="Important for interaction with PDHX and activity of
FT multienzyme pyruvate dehydrogenase complex"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT SITE 469
FT /note="Important for interaction with PDHX and activity of
FT multienzyme pyruvate dehydrogenase complex"
FT /evidence="ECO:0000250|UniProtKB:P09622"
FT DISULFID 78..83
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:P09624"
SQ SEQUENCE 504 AA; 54202 MW; 006E0252003A83A4 CRC64;
MLSQRLIGRT AVKSAFRPSG LPTVVNASRW RRGYATEADR DLVIIGGGVA GYVAAIKAGQ
EGMKVTCIEK RGTLGGTCLN VGCIPSKSLL NNSHLYHTIL HDTKHRGIEV GDVKLNLGQL
MKAKEQSVSG LTKGIEFLFK KNGVEYLKGT GSFEDPHTVK VELNDGGETR VTGKNILIAT
GSEVTPFPGL EIDEKTIISS TGALSLDHVP KKFLVIGGGI IGLEMASVWS RLGSEVTVVE
YLDQIGGPGM DTEISKNIQK ILKKQGINFK TGTKVLNGEK TGDGVKINVE AAKGGKPETL
EADVVLVAIG RRPYTKGLGL EKIGIELDER GRVIIDQEYR TKIPHIRCVG DATFGPMLAH
KAEEEAVAVV EYIKKGYGHV NYGCIPAVMY TFPEVAWVGQ SEQDLKKAGI PYRVGTFPFS
ANSRAKTNLD TEGFVKMLAD PETDRLLGIH IIGPNAGEMI AEGTLALEYG ASSEDIARTC
HAHPTLAEAF KEAAMATYSK AIHF
