HOSA_SULAC
ID HOSA_SULAC Reviewed; 468 AA.
AC Q4J989;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 89.
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=Saci_1304 {ECO:0000312|EMBL:AAY80642.1};
OS Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC
OS 15157 / NCIMB 11770).
OC Archaea; Crenarchaeota; Thermoprotei; Sulfolobales; Sulfolobaceae;
OC Sulfolobus.
OX NCBI_TaxID=330779;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770;
RX PubMed=15995215; DOI=10.1128/jb.187.14.4992-4999.2005;
RA Chen L., Bruegger K., Skovgaard M., Redder P., She Q., Torarinsson E.,
RA Greve B., Awayez M., Zibat A., Klenk H.-P., Garrett R.A.;
RT "The genome of Sulfolobus acidocaldarius, a model organism of the
RT Crenarchaeota.";
RL J. Bacteriol. 187:4992-4999(2005).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, ACTIVITY REGULATION,
RP PATHWAY, DOMAIN, AND DISRUPTION PHENOTYPE.
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. Does not display
CC 2-isopropylmalate synthase and citramalate synthase activities since it
CC cannot use 2-oxoisovalerate or pyruvate as substrate.
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:0000269|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 -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 1/5.
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. {ECO:0000269|PubMed:31330039}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene do not grow in MM without
CC or even with lysine, but grow in MM with the simultaneous
CC supplementation of lysine and arginine to the medium. Furthermore, the
CC mutant strain does not grow on MM supplemented with lysine and
CC glutamate, but grows with lysine and ornithine.
CC {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}.
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DR EMBL; CP000077; AAY80642.1; -; Genomic_DNA.
DR PDB; 6KTQ; X-ray; 1.98 A; A/B=1-382.
DR PDBsum; 6KTQ; -.
DR AlphaFoldDB; Q4J989; -.
DR SMR; Q4J989; -.
DR STRING; 330779.Saci_1304; -.
DR EnsemblBacteria; AAY80642; AAY80642; Saci_1304.
DR KEGG; sai:Saci_1304; -.
DR PATRIC; fig|330779.12.peg.1258; -.
DR eggNOG; arCOG02092; Archaea.
DR HOGENOM; CLU_022158_4_0_2; -.
DR OMA; DWSNGMR; -.
DR BRENDA; 2.3.3.14; 6160.
DR UniPathway; UPA00033; UER00028.
DR Proteomes; UP000001018; 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 3D-structure; Acyltransferase; Allosteric enzyme; Amino-acid biosynthesis;
KW Lysine biosynthesis; Magnesium; Manganese; Metal-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..468
FT /note="Homocitrate synthase"
FT /id="PRO_0000448052"
FT DOMAIN 11..266
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT ACT_SITE 299
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 19
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 20
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 83
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 143
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 177
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 205
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT BINDING 207
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O87198"
FT STRAND 9..15
FT /evidence="ECO:0007829|PDB:6KTQ"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 20..23
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 31..44
FT /evidence="ECO:0007829|PDB:6KTQ"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 58..72
FT /evidence="ECO:0007829|PDB:6KTQ"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 88..96
FT /evidence="ECO:0007829|PDB:6KTQ"
FT STRAND 100..107
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 110..115
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 121..137
FT /evidence="ECO:0007829|PDB:6KTQ"
FT STRAND 141..147
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 154..167
FT /evidence="ECO:0007829|PDB:6KTQ"
FT STRAND 170..176
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 183..196
FT /evidence="ECO:0007829|PDB:6KTQ"
FT STRAND 200..207
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 213..222
FT /evidence="ECO:0007829|PDB:6KTQ"
FT STRAND 227..231
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 244..255
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 265..276
FT /evidence="ECO:0007829|PDB:6KTQ"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:6KTQ"
FT TURN 289..292
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 297..305
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 315..318
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 332..342
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 348..359
FT /evidence="ECO:0007829|PDB:6KTQ"
FT HELIX 369..380
FT /evidence="ECO:0007829|PDB:6KTQ"
SQ SEQUENCE 468 AA; 51732 MW; B1C66520DDDCFBDE CRC64;
MLPKKKLHMK VGILDSTLRE GEQTPGVVFT TDQRVEIAKA LSDIGVQMIE AGHPAVSPDI
YEGIRRIIKL KREGVIKSEI VAHSRAVKRD IEVGAEIEAD RIAIFYGISD THLKAKHHTT
RDEALRSIAE TVSYAKSHGV KVRFTAEDAT RADYQYLLEV IKTVRDAGAD RVSIADTVGV
LYPSRTRELF KDLTSRFPDI EFDIHAHNDL GMAVANVLAA AEGGATIIHT TLNGLGERVG
IAPLQVVAAA LKYHFGIEVV DLKKLSEVAS LVEKYSGIAL PPNFPITGDY AFVHKAGVHV
AGVLNDPKTY EFLPPETFGR SRDYVIDKYT GKHAVKDRFD RLGVKLTDSE IDQVLAKIKS
NPNVRFYRDV DLLELAESVT GRILKPRPPE NIMALISVKC DSNVYTTSVT RRIVLIEGVR
EVMEISGDYD ILVKVEAKDS TELNQIIESI RAVKGVKSTL TSLILKKM
