ER10A_ASPFC
ID ER10A_ASPFC Reviewed; 433 AA.
AC B0XMC1;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Acetyl-CoA acetyltransferase erg10A, mitochondrial {ECO:0000303|PubMed:32005728};
DE EC=2.3.1.9 {ECO:0000269|PubMed:32005728};
DE AltName: Full=Acetoacetyl-CoA thiolase erg10A {ECO:0000303|PubMed:32005728};
DE AltName: Full=Ergosterol biosynthesis protein 10A {ECO:0000303|PubMed:32005728};
DE Flags: Precursor;
GN Name=erg10A {ECO:0000303|PubMed:32005728}; ORFNames=AFUB_000550;
OS Neosartorya fumigata (strain CEA10 / CBS 144.89 / FGSC A1163) (Aspergillus
OS fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=451804;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CEA10 / CBS 144.89 / FGSC A1163;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
RN [2] {ECO:0007744|PDB:6L2C, ECO:0007744|PDB:6L2G}
RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 36-432, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, BIOTECHNOLOGY, AND PATHWAY.
RX PubMed=32005728; DOI=10.1128/aem.02986-19;
RA Zhang Y., Wei W., Fan J., Jin C., Lu L., Fang W.;
RT "Characterization of Aspergillus fumigatus mitochondrial acetyl-CoA
RT acetyltransferase as an antifungal target.";
RL Appl. Environ. Microbiol. 0:0-0(2020).
CC -!- FUNCTION: Mitochondrial acetyl-CoA acetyltransferase that catalyzes
CC both the formation and degradation of acetoacetyl-CoA
CC (PubMed:32005728). Has no overlapping function with erg10B and seems
CC not to be involved in ergosterol biosynthesis (PubMed:32005728). Plays
CC an important role in growth, morphogenesis and maintaining
CC mitochondrial function including the response to oxidative stresses
CC (PubMed:32005728). {ECO:0000269|PubMed:32005728}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036,
CC ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.1.9;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10020,
CC ECO:0000269|PubMed:32005728};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21037;
CC Evidence={ECO:0000269|PubMed:32005728};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:Q4WCL5};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=26 uM for CoA {ECO:0000269|PubMed:32005728};
CC KM=43 uM for acetoacetyl-CoA {ECO:0000269|PubMed:32005728};
CC KM=232 uM for acetyl-CoA {ECO:0000269|PubMed:32005728};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 1/3.
CC {ECO:0000269|PubMed:32005728}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P41338}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:32005728}.
CC -!- DISRUPTION PHENOTYPE: Leads to lethality.
CC {ECO:0000269|PubMed:32005728}.
CC -!- BIOTECHNOLOGY: Mitochondrial erg10A is essential for A.fumigatus cell
CC viability and might be a potential drug target to feed the antifungal
CC drug development pipeline. {ECO:0000305|PubMed:32005728}.
CC -!- MISCELLANEOUS: Even though it is not involved in catalysis directly,
CC the Cl(-) anion stabilizes the catalytic site via both direct and
CC water-mediated hydrogen bonds to catalytic residues and residues
CC adjacent. {ECO:0000250|UniProtKB:Q4WCL5}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
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DR EMBL; DS499594; EDP55365.1; -; Genomic_DNA.
DR PDB; 6L2C; X-ray; 2.44 A; A/B/C/D=32-433.
DR PDB; 6L2G; X-ray; 2.41 A; A/B/C/D=36-432.
DR PDBsum; 6L2C; -.
DR PDBsum; 6L2G; -.
DR SMR; B0XMC1; -.
DR EnsemblFungi; EDP55365; EDP55365; AFUB_000550.
DR VEuPathDB; FungiDB:AFUB_000550; -.
DR HOGENOM; CLU_031026_0_1_1; -.
DR PhylomeDB; B0XMC1; -.
DR BRENDA; 2.3.1.9; 508.
DR UniPathway; UPA00058; UER00101.
DR Proteomes; UP000001699; Unassembled WGS sequence.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0003988; F:acetyl-CoA C-acyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR CDD; cd00751; thiolase; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR002155; Thiolase.
DR InterPro; IPR016039; Thiolase-like.
DR InterPro; IPR020615; Thiolase_acyl_enz_int_AS.
DR InterPro; IPR020610; Thiolase_AS.
DR InterPro; IPR020617; Thiolase_C.
DR InterPro; IPR020616; Thiolase_N.
DR Pfam; PF02803; Thiolase_C; 1.
DR Pfam; PF00108; Thiolase_N; 1.
DR PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR TIGRFAMs; TIGR01930; AcCoA-C-Actrans; 1.
DR PROSITE; PS00098; THIOLASE_1; 1.
DR PROSITE; PS00099; THIOLASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Metal-binding; Mitochondrion; Potassium;
KW Transferase; Transit peptide.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 35..433
FT /note="Acetyl-CoA acetyltransferase erg10A, mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000454145"
FT ACT_SITE 124
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT ACT_SITE 387
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT ACT_SITE 415
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT BINDING 219
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 229
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:32005728,
FT ECO:0007744|PDB:6L2C"
FT BINDING 262
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 280
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 284
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 416
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT STRAND 41..47
FT /evidence="ECO:0007829|PDB:6L2G"
FT TURN 56..59
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 101..107
FT /evidence="ECO:0007829|PDB:6L2G"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 115..121
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 144..154
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 179..184
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 193..203
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 208..227
FT /evidence="ECO:0007829|PDB:6L2G"
FT TURN 228..234
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 260..265
FT /evidence="ECO:0007829|PDB:6L2G"
FT TURN 280..282
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 287..296
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 298..304
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 312..321
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 324..329
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 330..342
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 349..354
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 359..368
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 374..377
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 382..385
FT /evidence="ECO:0007829|PDB:6L2G"
FT HELIX 389..401
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 409..416
FT /evidence="ECO:0007829|PDB:6L2G"
FT TURN 417..419
FT /evidence="ECO:0007829|PDB:6L2G"
FT STRAND 420..428
FT /evidence="ECO:0007829|PDB:6L2G"
SQ SEQUENCE 433 AA; 45710 MW; 4D5B4C442DAAABA0 CRC64;
MAIQTTTGLA ARLVAKRATF PASRRNFSAS RSALKEIQEA YILSGARTPT AKFNGSFVSV
SAPELGAVAI KSAVSKSGVP VEKITDVYMG NVLQGAVGQA PARQASMFAG LSPTVESMTV
NKVCASGLKA VALAAQNIQL GLAEAQVAGG MENMSRVPYY LPRSTQLPPF GEIKLQDGLI
QDGLWDVYNQ FHMGICAEKT AKKYEISREE QDQYAIQSYQ RAQAAWKENK FAEEIAPVTV
KGKKGETVVE RDEGYENLRI DKMATLKPAF LRDGTGTVTA GNASTMNDGA SALVLGSKAI
AREFAQGNRA LARIVSTADA AIDPVDFPVA PAKAVPIALE RAGITKDQVA VWEFNEAFAA
VIKANEKILG LQNARVNPLG GAISLGHALG SSGSRILVTL LHQLQPGEYG VAAICNGGGA
ATAMVVQKLD RVD
