TASA_HAPIR
ID TASA_HAPIR Reviewed; 270 AA.
AC A0A0F7GG11;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=4-hydroxy-4-methyl-2-oxoglutarate aldolase tasA {ECO:0000303|PubMed:25885659};
DE EC=4.1.3.17 {ECO:0000269|PubMed:25885659};
DE AltName: Full=Tetramic acid Sch210971/2 biosynthesis cluster protein A {ECO:0000303|PubMed:25885659};
GN Name=tasA {ECO:0000303|PubMed:25885659};
OS Hapsidospora irregularis.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreales incertae sedis; Hapsidospora.
OX NCBI_TaxID=95324;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=25885659; DOI=10.1021/acs.orglett.5b00715;
RA Kakule T.B., Zhang S., Zhan J., Schmidt E.W.;
RT "Biosynthesis of the tetramic acids Sch210971 and Sch210972.";
RL Org. Lett. 17:2295-2297(2015).
CC -!- FUNCTION: 4-hydroxy-4-methyl-2-oxoglutarate aldolase; part of the gene
CC cluster that mediates the biosynthesis of the tetramic acids Sch210971
CC and Sch210972, potential anti-HIV fungal natural product that contain a
CC decalin core (PubMed:25885659). The PKS module of tasS together with
CC the enoylreductase tasC catalyze the formation of the polyketide unit
CC which is then conjugated to 4-hydroxyl-4-methyl glutamate (HMG) by the
CC condensation domain of the tasS NRPS module (PubMed:25885659). One
CC unique structural feature of Sch210971 and Sch210972 is the tetramic
CC acid motif proposed to be derived from the non-proteinogenic amino acid
CC HMG, by a Dieckmann-type condensation catalyzed by the reductase domain
CC of tasS (PubMed:25885659). The aldolase tasA catalyzes the aldol
CC condensation of 2 molecules of pyruvic acid to yield the intermediate
CC 4-hydroxyl-4-methyl-2-oxoglutarate (HMOG), which can then be
CC stereoselectively transaminated, may be by tasG, to form HMG
CC (PubMed:25885659). The Diels-Alderase tas3 then uses the Dieckmann
CC product of tasS as substrate and catalyzes the Diels-Alder
CC cycloaddition to form the decalin ring of Sch210971 and Sch210972
CC (PubMed:25885659). {ECO:0000269|PubMed:25885659}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxy-4-methyl-2-oxoglutarate = 2 pyruvate;
CC Xref=Rhea:RHEA:22748, ChEBI:CHEBI:15361, ChEBI:CHEBI:58276;
CC EC=4.1.3.17; Evidence={ECO:0000269|PubMed:25885659};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22750;
CC Evidence={ECO:0000269|PubMed:25885659};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000250|UniProtKB:Q47098};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q47098};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q47098};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q47098};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q47098};
CC Note=Binds 1 divalent metal cation per subunit.
CC {ECO:0000250|UniProtKB:Q47098};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25885659}.
CC -!- SUBUNIT: Homohexamer; trimer of dimers. {ECO:0000250|UniProtKB:Q47098}.
CC -!- SIMILARITY: Belongs to the HpcH/HpaI aldolase family. {ECO:0000305}.
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DR EMBL; KP835202; AKG54861.1; -; Genomic_DNA.
DR SMR; A0A0F7GG11; -.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 3.20.20.60; -; 1.
DR InterPro; IPR005000; Aldolase/citrate-lyase_domain.
DR InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom.
DR InterPro; IPR040442; Pyrv_Kinase-like_dom_sf.
DR Pfam; PF03328; HpcH_HpaI; 1.
DR SUPFAM; SSF51621; SSF51621; 1.
PE 1: Evidence at protein level;
KW Cobalt; Iron; Lyase; Magnesium; Manganese; Metal-binding; Zinc.
FT CHAIN 1..270
FT /note="4-hydroxy-4-methyl-2-oxoglutarate aldolase tasA"
FT /id="PRO_0000453346"
FT ACT_SITE 49
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT BINDING 156
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT BINDING 182
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT BINDING 182
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT SITE 74
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT SITE 89
FT /note="Increases basicity of active site His"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
SQ SEQUENCE 270 AA; 28621 MW; 39C163F30BFEEAAC CRC64;
MVAYENVLAN KASSGRLCKA LGIRLVTNPL VVQLAKNAGF DALFIDLEHS TLSLADASAI
ACAGLLSGLT PFVRVPYQCG MGFVQQVLDG GAMGIIFPHV HTAADARAAV DTCKFPPHGR
RSMWGQQPVL GLRVTPLHKI AEVCDRVASS VVVMIEAADS IEQADAIAAV EGVDVLLVGC
IDLSTDMGIA GNFESKRFRA ALEAVSAACH RHGKLMGLAG LYNNRKLQEW AVHSLRARFI
LCQQDSNLLA LGAMECAGAV ASIQLDRCPD
