HOSA_SULTO
ID HOSA_SULTO Reviewed; 460 AA.
AC Q971S5;
DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Homocitrate synthase {ECO:0000303|PubMed:31330039};
DE Short=HCS {ECO:0000303|PubMed:31330039};
DE EC=2.3.3.14 {ECO:0000269|PubMed:31330039};
GN OrderedLocusNames=STK_13010;
OS Sulfurisphaera tokodaii (strain DSM 16993 / JCM 10545 / NBRC 100140 / 7)
OS (Sulfolobus tokodaii).
OC Archaea; Crenarchaeota; Thermoprotei; Sulfolobales; Sulfolobaceae;
OC Sulfurisphaera.
OX NCBI_TaxID=273063;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 16993 / JCM 10545 / NBRC 100140 / 7;
RX PubMed=11572479; DOI=10.1093/dnares/8.4.123;
RA Kawarabayasi Y., Hino Y., Horikawa H., Jin-no K., Takahashi M., Sekine M.,
RA Baba S., Ankai A., Kosugi H., Hosoyama A., Fukui S., Nagai Y.,
RA Nishijima K., Otsuka R., Nakazawa H., Takamiya M., Kato Y., Yoshizawa T.,
RA Tanaka T., Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K.,
RA Masuda S., Yanagii M., Nishimura M., Yamagishi A., Oshima T., Kikuchi H.;
RT "Complete genome sequence of an aerobic thermoacidophilic Crenarchaeon,
RT Sulfolobus tokodaii strain7.";
RL DNA Res. 8:123-140(2001).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, PATHWAY, DOMAIN, AND SUBUNIT.
RX PubMed=31330039; DOI=10.1002/1873-3468.13550;
RA Suzuki T., Akiyama N., Yoshida A., Tomita T., Lassak K., Haurat M.F.,
RA Okada T., Takahashi K., Albers S.V., Kuzuyama T., Nishiyama M.;
RT "Biochemical characterization of archaeal homocitrate synthase from
RT Sulfolobus acidocaldarius.";
RL FEBS Lett. 594:126-134(2020).
CC -!- FUNCTION: Catalyzes the aldol-type condensation of 2-oxoglutarate with
CC acetyl-CoA to yield homocitrate. Carries out the first step of the
CC alpha-aminoadipate (AAA) lysine biosynthesis pathway.
CC {ECO:0000269|PubMed:31330039}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + acetyl-CoA + H2O = (2R)-homocitrate + CoA +
CC H(+); Xref=Rhea:RHEA:12929, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:58884; EC=2.3.3.14;
CC Evidence={ECO:0000269|PubMed:31330039};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12930;
CC Evidence={ECO:0000305|PubMed:31330039};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O87198};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:O87198};
CC -!- ACTIVITY REGULATION: Inhibited by lysine.
CC {ECO:0000269|PubMed:31330039}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.7 uM for 2-oxoglutarate {ECO:0000269|PubMed:31330039};
CC KM=2.6 uM for acetyl-CoA {ECO:0000269|PubMed:31330039};
CC Note=kcat is 1.4 sec(-1). {ECO:0000269|PubMed:31330039};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 1/5.
CC {ECO:0000305|PubMed:31330039}.
CC -!- SUBUNIT: Forms a homotetramer in the absence of lysine, and is in
CC hexadecamer-octamer equilibrium in the presence of lysine.
CC {ECO:0000269|PubMed:31330039}.
CC -!- DOMAIN: Contains an N-terminal catalytic domain fused with a RAM
CC (Regulation of Amino acid Metabolism) domain at the C-terminus. The
CC mutant enzyme lacking the RAM domain is insensitive to inhibition by
CC lysine, indicating that the RAM domain is responsible for enzyme
CC allosteric regulation. Moreover, the mutant enzyme lacking the RAM
CC domain forms homodimer irrespective of the presence of lysine, which
CC suggests that HCS undergoes changes in its oligomeric state by binding
CC lysine at its RAM domain. {ECO:0000269|PubMed:31330039}.
CC -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC family. Homocitrate synthase LYS20/LYS21 subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_02222, ECO:0000305}.
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DR EMBL; BA000023; BAB66345.1; -; Genomic_DNA.
DR RefSeq; WP_010979323.1; NC_003106.2.
DR AlphaFoldDB; Q971S5; -.
DR SMR; Q971S5; -.
DR STRING; 273063.STK_13010; -.
DR EnsemblBacteria; BAB66345; BAB66345; STK_13010.
DR GeneID; 42801089; -.
DR KEGG; sto:STK_13010; -.
DR PATRIC; fig|273063.9.peg.1464; -.
DR eggNOG; arCOG02092; Archaea.
DR OMA; DWSNGMR; -.
DR OrthoDB; 10632at2157; -.
DR UniPathway; UPA00033; UER00028.
DR Proteomes; UP000001015; Chromosome.
DR GO; GO:0004410; F:homocitrate synthase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IEA:UniProtKB-UniRule.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_02222; Homocitr_synth_fung_arch; 1.
DR InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR011008; Dimeric_a/b-barrel.
DR InterPro; IPR011872; Homocitrate_synth_fun/arc.
DR InterPro; IPR000891; PYR_CT.
DR InterPro; IPR019887; Tscrpt_reg_AsnC/Lrp_C.
DR Pfam; PF01037; AsnC_trans_reg; 1.
DR Pfam; PF00682; HMGL-like; 1.
DR SUPFAM; SSF54909; SSF54909; 1.
DR TIGRFAMs; TIGR02146; LysS_fung_arch; 1.
DR PROSITE; PS00816; AIPM_HOMOCIT_SYNTH_2; 1.
DR PROSITE; PS50991; PYR_CT; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Allosteric enzyme; Amino-acid biosynthesis;
KW Lysine biosynthesis; Magnesium; Manganese; Metal-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..460
FT /note="Homocitrate synthase"
FT /id="PRO_0000140426"
FT DOMAIN 3..258
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT ACT_SITE 291
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 11
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 12
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 75
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 135
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 169
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 197
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 199
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
SQ SEQUENCE 460 AA; 50510 MW; C558B21F2AD179CB CRC64;
MKVGILDSTL REGEQTPGVV FTIDQRVEIA KALSDVGVQM IEAGHPAVSS DIYEGIKRIM
KLKREGLITS EIVGHSRAVK KDIEVAAELE VDRIAIFYGV SDIHLKAKHH VTREEALNII
AETISYAKSH GVKVRFTAED GSRTDLDYLI KVCKTARDAG ADRVSIADTV GILYPTKTRE
LFSTLVREVP GLEFDIHAHN DLGLAVANAL AAIEGGATII HTTVNGLGER VGIVPLQVIA
AAIKYHFGIE VVKLNKLQQL ASLVEKYSGI PMPPNYPITG DYAFIHKAGI HVAGVLNDPS
TYEFMPPETF GRSRDYVIDK YTGKHALKDR FEKLGVKLSD VELDQVLAKI KSNPNVRFYR
DVDLLEIAES VTGRVLKPKP PENIEALISV KCESNVYTTA VTRRLSVIPG VKEVMEISGD
YDILVKVEAK DPNELNQIIE NIRAVKGVSS TLTSLVLKKM
