ODP2_CHATD
ID ODP2_CHATD Reviewed; 459 AA.
AC G0S4X6;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial {ECO:0000303|PubMed:33567276};
DE EC=2.3.1.12 {ECO:0000269|PubMed:33567276};
DE AltName: Full=Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex {ECO:0000303|PubMed:33567276};
DE AltName: Full=MRP3 {ECO:0000305};
DE AltName: Full=Pyruvate dehydrogenase complex component E2 {ECO:0000303|PubMed:33567276};
DE Short=PDC-E2 {ECO:0000305};
DE Short=PDCE2 {ECO:0000305};
DE Flags: Precursor;
GN ORFNames=CTHT_0032020;
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] {ECO:0007744|PDB:7BGJ}
RP STRUCTURE BY ELECTRON MICROSCOPY (6.90 ANGSTROMS), FUNCTION, CATALYTIC
RP ACTIVITY, 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 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] {ECO:0007744|PDB:7OTT}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.84 ANGSTROMS) OF THE PYRUVATE
RP DEHYDROGENASE COMPLEX E2 CORE, FUNCTION, AND DOMAIN.
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).
RN [4] {ECO:0007744|PDB:7Q5Q, ECO:0007744|PDB:7Q5R, ECO:0007744|PDB:7Q5S}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.84 ANGSTROMS) OF THE PYRUVATE
RP DEHYDROGENASE COMPLEX E2 CORE, FUNCTION, AND DOMAIN.
RX PubMed=35093201; DOI=10.1016/j.str.2022.01.001;
RA Skalidis I., Kyrilis F.L., Tueting C., Hamdi F., Chojnowski G.,
RA Kastritis P.L.;
RT "Cryo-EM and artificial intelligence visualize endogenous protein community
RT members.";
RL Structure 0:0-0(2022).
CC -!- FUNCTION: The 10-megadalton pyruvate dehydrogenase complex contains
CC multiple copies of three enzymatic components: pyruvate dehydrogenase
CC (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide
CC dehydrogenase (E3) and catalyzes the overall oxidative decarboxylation
CC of pyruvate to form acetyl-CoA and CO(2) (PubMed:33567276,
CC PubMed:34836937, PubMed:35093201). Within the complex, pyruvate and
CC thiamine pyrophosphate (TPP or vitamin B1) are bound by pyruvate
CC dehydrogenase E1 subunits alpha and beta and pyruvate is decarboxylated
CC leading to the 2-carbon hydrohyethyl bound to TPP. The E2 component
CC contains covalently-bound lipoyl cofactors and transfers the
CC 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:0000269|PubMed:33567276, ECO:0000269|PubMed:34836937,
CC ECO:0000269|PubMed:35093201, ECO:0000305|PubMed:33567276}.
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 Evidence={ECO:0000269|PubMed:33567276};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17019;
CC Evidence={ECO:0000269|PubMed:33567276};
CC -!- COFACTOR:
CC Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01066};
CC Note=Binds 1 lipoyl cofactor covalently. {ECO:0000255|PROSITE-
CC ProRule:PRU01066};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=68 uM for coenzyme A {ECO:0000269|PubMed:33567276};
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 -!- DOMAIN: The peripheral subunit binding domain (PBSD), serves as a
CC selective binding site for other domains of the E1 and E3 subunits.
CC {ECO:0000305|PubMed:34836937}.
CC -!- DOMAIN: The C-terminal catalytic domain catalyzes the transfer of
CC acetyl groups and acetyl-CoA synthesis. {ECO:0000305|PubMed:34836937}.
CC -!- DOMAIN: The loop element facing inside the core cavity formed by
CC residues Val-405 to Trp-420 is potentially critical for the
CC organization of the PDH complex core scaffold.
CC {ECO:0000269|PubMed:35093201}.
CC -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; GL988041; EGS21347.1; -; Genomic_DNA.
DR RefSeq; XP_006693643.1; XM_006693580.1.
DR PDB; 7BGJ; EM; 6.90 A; A=1-459.
DR PDB; 7OTT; EM; 3.85 A; A=1-459.
DR PDB; 7Q5Q; EM; 3.85 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y=1-459.
DR PDB; 7Q5R; EM; 3.85 A; A/AA/AB/B/BA/BB/C/CA/CB/D/DA/DB/E/EA/EB/F/FA/FB/G/GA/GB/H/HA/HB/I/IA/IB/J/JA/K/KA/L/LA/M/MA/N/NA/O/OA/P/PA/Q/QA/R/RA/S/SA/T/TA/U/UA/V/VA/W/WA/X/XA/Y/YA/Z/ZA=1-459.
DR PDB; 7Q5S; EM; 3.85 A; A/B/C/D/E/F/G/H/I/J/K=1-459.
DR PDBsum; 7BGJ; -.
DR PDBsum; 7OTT; -.
DR PDBsum; 7Q5Q; -.
DR PDBsum; 7Q5R; -.
DR PDBsum; 7Q5S; -.
DR SMR; G0S4X6; -.
DR STRING; 759272.G0S4X6; -.
DR EnsemblFungi; EGS21347; EGS21347; CTHT_0032020.
DR GeneID; 18257240; -.
DR KEGG; cthr:CTHT_0032020; -.
DR eggNOG; KOG0557; Eukaryota.
DR HOGENOM; CLU_016733_10_2_1; -.
DR OrthoDB; 747232at2759; -.
DR Proteomes; UP000008066; Unassembled WGS sequence.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0045254; C:pyruvate dehydrogenase complex; IEA:InterPro.
DR GO; GO:0004742; F:dihydrolipoyllysine-residue acetyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; IEA:InterPro.
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; IPR000089; Biotin_lipoyl.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR045257; E2/Pdx1.
DR InterPro; IPR036625; E3-bd_dom_sf.
DR InterPro; IPR006257; LAT1.
DR InterPro; IPR004167; PSBD.
DR InterPro; IPR011053; Single_hybrid_motif.
DR PANTHER; PTHR23151; PTHR23151; 1.
DR Pfam; PF00198; 2-oxoacid_dh; 1.
DR Pfam; PF00364; Biotin_lipoyl; 1.
DR Pfam; PF02817; E3_binding; 1.
DR SUPFAM; SSF47005; SSF47005; 1.
DR SUPFAM; SSF51230; SSF51230; 1.
DR TIGRFAMs; TIGR01349; PDHac_trf_mito; 1.
DR PROSITE; PS50968; BIOTINYL_LIPOYL; 1.
DR PROSITE; PS00189; LIPOYL; 1.
DR PROSITE; PS51826; PSBD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Lipoyl; Mitochondrion; Pyruvate;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 29..459
FT /note="Dihydrolipoyllysine-residue acetyltransferase
FT component of pyruvate dehydrogenase complex, mitochondrial"
FT /id="PRO_0000456222"
FT DOMAIN 34..110
FT /note="Lipoyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 177..214
FT /note="Peripheral subunit-binding (PSBD)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01170"
FT BINDING 269
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:34836937,
FT ECO:0007744|PDB:7OTT"
FT BINDING 283
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:34836937,
FT ECO:0007744|PDB:7OTT"
FT BINDING 285
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:34836937,
FT ECO:0007744|PDB:7OTT"
FT BINDING 357
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:34836937,
FT ECO:0007744|PDB:7OTT"
FT BINDING 374
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:34836937,
FT ECO:0007744|PDB:7OTT"
FT BINDING 375
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:34836937,
FT ECO:0007744|PDB:7OTT"
FT SITE 384
FT /note="May form a delocalized pi-electron network with Arg-
FT 384 of 2 other E2 subunits within the complex, which
FT greatly improves protein stability"
FT /evidence="ECO:0000269|PubMed:34836937,
FT ECO:0007744|PDB:7OTT"
FT MOD_RES 75
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
SQ SEQUENCE 459 AA; 48721 MW; 6194FC0E279FD6D6 CRC64;
MLAQVLRRQA LQHVRLARAA APSLTRWYAS YPPHTIVKMP ALSPTMTSGN IGAWQKKPGD
AITPGEVLVE IETDKAQMDF EFQEEGVLAK ILKETGEKDV AVGSPIAVLV EEGTDINAFQ
NFTLEDAGGD AAAPAAPAKE ELAKAETAPT PASTSAPEPE ETTSTGKLEP ALDREPNVSF
AAKKLAHELD VPLKALKGTG PGGKITEEDV KKAASAPAAA AAAPGAAYQD IPISNMRKTI
ATRLKESVSE NPHFFVTSEL SVSKLLKLRQ ALNSSAEGRY KLSVNDFLIK AIAVACKRVP
AVNSSWRDGV IRQFDTVDVS VAVATPTGLI TPIVKGVEAK GLETISATVK ELAKKARDGK
LKPEDYQGGT ISISNMGMNP AVERFTAIIN PPQAAILAVG TTKKVAVPVE NEDGTTGVEW
DDQIVVTASF DHKVVDGAVG AEWMRELKKV VENPLELLL
