CGHB_CHAGB
ID CGHB_CHAGB Reviewed; 269 AA.
AC Q2HBN5;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=4-hydroxy-4-methyl-2-oxoglutarate aldolase cghB {ECO:0000303|PubMed:26360642};
DE EC=4.1.3.17 {ECO:0000269|PubMed:26360642};
DE AltName: Full=Sch210972 biosynthesis cluster protein B {ECO:0000303|PubMed:26360642};
GN Name=cghB {ECO:0000303|PubMed:26360642}; ORFNames=CHGG_02369;
OS Chaetomium globosum (strain ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 /
OS NRRL 1970) (Soil fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Chaetomium.
OX NCBI_TaxID=306901;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 / NRRL 1970;
RX PubMed=25720678; DOI=10.1128/genomea.00021-15;
RA Cuomo C.A., Untereiner W.A., Ma L.-J., Grabherr M., Birren B.W.;
RT "Draft genome sequence of the cellulolytic fungus Chaetomium globosum.";
RL Genome Announc. 3:E0002115-E0002115(2015).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26360642; DOI=10.1002/cbic.201500386;
RA Sato M., Yagishita F., Mino T., Uchiyama N., Patel A., Chooi Y.H., Goda Y.,
RA Xu W., Noguchi H., Yamamoto T., Hotta K., Houk K.N., Tang Y., Watanabe K.;
RT "Involvement of lipocalin-like CghA in decalin-forming stereoselective
RT intramolecular [4+2] cycloaddition.";
RL ChemBioChem 16:2294-2298(2015).
CC -!- FUNCTION: 4-hydroxy-4-methyl-2-oxoglutarate aldolase; part of the gene
CC cluster that mediates the biosynthesis of the tetramic acid Sch210972,
CC a potential anti-HIV fungal natural product that contains a decalin
CC core (PubMed:26360642). The PKS module of cghG together with the
CC enoylreductase cghC catalyze the formation of the polyketide unit which
CC is then conjugated to 4-hydroxyl-4-methyl glutamate (HMG) by the
CC condensation domain of the cghG NRPS module (PubMed:26360642). One
CC unique structural feature of Sch210972 is the tetramic acid motif
CC proposed to be derived from the non-proteinogenic amino acid HMG, by a
CC Dieckmann-type condensation catalyzed by the reductase domain of cghG
CC (PubMed:26360642). The aldolase cghB catalyzes the aldol condensation
CC of 2 molecules of pyruvic acid to yield the intermediate 4-hydroxyl-4-
CC methyl-2-oxoglutarate (HMOG), which can then be stereoselectively
CC transaminated by an unidentified enzyme to form HMG (PubMed:26360642).
CC The Diels-Alderase cghA then uses the Dieckmann product released by
CC cghG as substrate and catalyzes the Diels-Alder cycloaddition to form
CC the decalin ring of Sch210972 (PubMed:26360642). CghA also suppresses
CC the nonenzymatic formation of the alternative stereoisomer
CC (PubMed:26360642). {ECO:0000269|PubMed:26360642}.
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:26360642};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22750;
CC Evidence={ECO:0000269|PubMed:26360642};
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:26360642}.
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; CH408030; EAQ90434.1; -; Genomic_DNA.
DR RefSeq; XP_001228885.1; XM_001228884.1.
DR SMR; Q2HBN5; -.
DR STRING; 306901.Q2HBN5; -.
DR EnsemblFungi; EAQ90434; EAQ90434; CHGG_02369.
DR GeneID; 4388354; -.
DR eggNOG; ENOG502SJZ2; Eukaryota.
DR HOGENOM; CLU_059964_4_0_1; -.
DR InParanoid; Q2HBN5; -.
DR OMA; KYPPQGC; -.
DR OrthoDB; 1342057at2759; -.
DR Proteomes; UP000001056; Unassembled WGS sequence.
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;
KW Reference proteome; Zinc.
FT CHAIN 1..269
FT /note="4-hydroxy-4-methyl-2-oxoglutarate aldolase cghB"
FT /id="PRO_0000453345"
FT ACT_SITE 48
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT BINDING 155
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT BINDING 181
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT SITE 73
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
FT SITE 88
FT /note="Increases basicity of active site His"
FT /evidence="ECO:0000250|UniProtKB:Q47098"
SQ SEQUENCE 269 AA; 28272 MW; 351D7DD8620265FB CRC64;
MASFNNVLTK AAAGRLCKAM GVRMVANPLV VQLAANAGFE ALFIDLEHST LSLADASAIA
CAGLLSGLTP LVRVPYQCGI GFVQQALDGG AMGIVFPHIH TAADARAAVQ TCKFPPLGVR
SMWGQQPALG MRVTAIGRIV EVCNAAASSV IVMIEAASSI ENIEAIAAVE GVDVLLVGCL
DLSTDMGMPG RFETRAFRTA LEKVSAACRH SGKTMGLAGI YNNRELHEWA INTLNVRFML
CQQDSNLLAM AAVDCASAVA KIDRARLLN
