ER10B_ASPFC
ID ER10B_ASPFC Reviewed; 398 AA.
AC B0YA65;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Acetyl-CoA acetyltransferase erg10B, cytosolic {ECO:0000303|Ref.5};
DE EC=2.3.1.9 {ECO:0000269|Ref.5};
DE AltName: Full=Acetoacetyl-CoA thiolase erg10B {ECO:0000303|Ref.5};
DE Short=ACAT {ECO:0000303|Ref.5};
DE AltName: Full=Cytosolic thiolase erg10B {ECO:0000303|Ref.5};
DE Short=CT {ECO:0000303|Ref.5};
DE AltName: Full=Ergosterol biosynthesis protein 10B {ECO:0000303|PubMed:17352532};
GN Name=erg10B {ECO:0000303|PubMed:32005728}; ORFNames=AFUB_083570;
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]
RP IDENTIFICATION, AND FUNCTION.
RX PubMed=16110826; DOI=10.1080/13693780400029114;
RA Ferreira M.E., Colombo A.L., Paulsen I., Ren Q., Wortman J., Huang J.,
RA Goldman M.H., Goldman G.H.;
RT "The ergosterol biosynthesis pathway, transporter genes, and azole
RT resistance in Aspergillus fumigatus.";
RL Med. Mycol. 43:S313-S319(2005).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=17352532; DOI=10.1371/journal.ppat.0030024;
RA Hu W., Sillaots S., Lemieux S., Davison J., Kauffman S., Breton A.,
RA Linteau A., Xin C., Bowman J., Becker J., Jiang B., Roemer T.;
RT "Essential gene identification and drug target prioritization in
RT Aspergillus fumigatus.";
RL PLoS Pathog. 3:e24-e24(2007).
RN [4]
RP FUNCTION.
RX PubMed=22106303; DOI=10.1073/pnas.1106399108;
RA Yasmin S., Alcazar-Fuoli L., Gruendlinger M., Puempel T., Cairns T.,
RA Blatzer M., Lopez J.F., Grimalt J.O., Bignell E., Haas H.;
RT "Mevalonate governs interdependency of ergosterol and siderophore
RT biosyntheses in the fungal pathogen Aspergillus fumigatus.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E497-E504(2012).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND
RP ACTIVITY REGULATION.
RX DOI=10.1021/acscatal.7b02873;
RA Marshall A.C., Bond C.S., Bruning J.B.;
RT "Structure of Aspergillus fumigatus cytosolic thiolase: trapped tetrahedral
RT reaction intermediates and activation by monovalent cations.";
RL ACS Catal. 8:1973-1989(2018).
RN [6]
RP FUNCTION.
RX PubMed=30940706; DOI=10.1128/mbio.00437-19;
RA Rybak J.M., Ge W., Wiederhold N.P., Parker J.E., Kelly S.L., Rogers P.D.,
RA Fortwendel J.R.;
RT "Mutations in hmg1, challenging the paradigm of clinical triazole
RT resistance in Aspergillus fumigatus.";
RL MBio 10:0-0(2019).
RN [7]
RP IDENTIFICATION.
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: Acetyl-CoA acetyltransferase; part of the first module of
CC ergosterol biosynthesis pathway that includes the early steps of the
CC pathway, conserved across all eukaryotes, and which results in the
CC formation of mevalonate from acetyl-coenzyme A (acetyl-CoA)
CC (PubMed:32005728) (Probable). In this module, the cytosolic acetyl-CoA
CC acetyltransferase erg10B catalyzes the formation of acetoacetyl-CoA
CC (PubMed:32005728). The hydroxymethylglutaryl-CoA synthases AFUA_8G07210
CC and AFUA_3G10660 then condense acetyl-CoA with acetoacetyl-CoA to form
CC HMG-CoA (Probable). The rate-limiting step of the early module is the
CC reduction to mevalonate by the 3-hydroxy-3-methylglutaryl-coenzyme A
CC (HMG-CoA) reductases hmg1 and hmg2 (PubMed:22106303, PubMed:30940706).
CC Mevalonate is also a precursor for the extracellular siderophore
CC triacetylfusarinine C (TAFC) (PubMed:22106303).
CC {ECO:0000269|PubMed:22106303, ECO:0000269|PubMed:30940706,
CC ECO:0000269|PubMed:32005728, ECO:0000305|PubMed:16110826}.
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, ECO:0000269|Ref.5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21037;
CC Evidence={ECO:0000269|Ref.5};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103; Evidence={ECO:0000269|Ref.5};
CC -!- ACTIVITY REGULATION: Activity is increased by monovalent cations such
CC as K(+), Rb(+) or Cs(+). {ECO:0000269|Ref.5}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=42 uM for acetoacetyl-CoA (in law salt conditions)
CC {ECO:0000269|Ref.5};
CC KM=8 uM for acetoacetyl-CoA (in the presence of 100 mM NaCl)
CC {ECO:0000269|Ref.5};
CC KM=8 uM for acetoacetyl-CoA (in the presence of 100 mM KCl)
CC {ECO:0000269|Ref.5};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 1/3.
CC {ECO:0000269|Ref.5}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|Ref.5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:32005728}.
CC -!- DISRUPTION PHENOTYPE: Leads to lethality. {ECO:0000269|PubMed:17352532,
CC ECO:0000269|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; DS499600; EDP48908.1; -; Genomic_DNA.
DR SMR; B0YA65; -.
DR EnsemblFungi; EDP48908; EDP48908; AFUB_083570.
DR VEuPathDB; FungiDB:AFUB_083570; -.
DR HOGENOM; CLU_031026_0_1_1; -.
DR PhylomeDB; B0YA65; -.
DR UniPathway; UPA00058; UER00101.
DR Proteomes; UP000001699; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016126; P:sterol biosynthetic process; 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; IPR020617; Thiolase_C.
DR InterPro; IPR020613; Thiolase_CS.
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; PS00737; THIOLASE_2; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Cytoplasm; Lipid biosynthesis; Lipid metabolism;
KW Metal-binding; Potassium; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..398
FT /note="Acetyl-CoA acetyltransferase erg10B, cytosolic"
FT /id="PRO_0000454147"
FT ACT_SITE 92
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT ACT_SITE 354
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT ACT_SITE 384
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT BINDING 187
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:0000250|UniProtKB:Q4WCL5"
FT BINDING 232
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 249
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 250
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 252
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 253
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 350
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
FT BINDING 385
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q4WCL5"
SQ SEQUENCE 398 AA; 40909 MW; 648C2196D8C00BC8 CRC64;
MSSLPAVYIV SSARTPVGSF LGSLSSLTAP QLGAHAIKAA LAKVDGLKPS DVQEVFFGNV
ISANVGQNPA RQCALGAGLE ESTICTTVNK VCASGLKAII LGAQTIMTGN ADVVVAGGTE
SMSNAPHYLP NLRTGAKYGH QSLVDGIMKD GLTDAGKQEL MGLQAEECAQ DHGFSREQQD
EYAIRTYEKA QAAQKAGLFD EEIAPIQLPG FRGKPDVTVT QDEEPKNLNP EKLRAIKPAF
IPGSGTVTAP NSSPLNDGAA AVVLVSEAKL KELNLKPVAK ILGWGDAAQQ PSKFTTAPAL
AIPKALKHAG VGQDAIDAFE INEAFSVVAL ANMKLLGIPE EKVNLHGGAV AIGHPIGASG
ARILTTLLGV LKAKKGKLGC AGICNGGGGA SALVVELL
