HACA_THET2
ID HACA_THET2 Reviewed; 418 AA.
AC Q9ZNE0; O87199;
DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Homoaconitase large subunit;
DE Short=HACN;
DE EC=4.2.1.36;
DE AltName: Full=Homoaconitate hydratase;
GN Name=hacA; Synonyms=lys4A, lysT; OrderedLocusNames=TT_C1547;
OS Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27).
OC Bacteria; Deinococcus-Thermus; Deinococci; Thermales; Thermaceae; Thermus.
OX NCBI_TaxID=262724;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10074061; DOI=10.1128/jb.181.6.1713-1718.1999;
RA Kobashi N., Nishiyama M., Tanokura M.;
RT "Aspartate kinase-independent lysine synthesis in an extremely thermophilic
RT bacterium, Thermus thermophilus: lysine is synthesized via alpha-
RT aminoadipic acid not via diaminopimelic acid.";
RL J. Bacteriol. 181:1713-1718(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-163 / DSM 7039 / HB27;
RX PubMed=15064768; DOI=10.1038/nbt956;
RA Henne A., Brueggemann H., Raasch C., Wiezer A., Hartsch T., Liesegang H.,
RA Johann A., Lienard T., Gohl O., Martinez-Arias R., Jacobi C.,
RA Starkuviene V., Schlenczeck S., Dencker S., Huber R., Klenk H.-P.,
RA Kramer W., Merkl R., Gottschalk G., Fritz H.-J.;
RT "The genome sequence of the extreme thermophile Thermus thermophilus.";
RL Nat. Biotechnol. 22:547-553(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-388.
RX PubMed=9868782; DOI=10.1111/j.1574-6968.1998.tb13341.x;
RA Kosuge T., Hoshino T.;
RT "Lysine is synthesized through the alpha-aminoadipate pathway in Thermus
RT thermophilus.";
RL FEMS Microbiol. Lett. 169:361-367(1998).
RN [4]
RP ROLE IN LYSINE BIOSYNTHESIS, AND PATHWAY.
RX PubMed=10613839; DOI=10.1101/gr.9.12.1175;
RA Nishida H., Nishiyama M., Kobashi N., Kosuge T., Hoshino T., Yamane H.;
RT "A prokaryotic gene cluster involved in synthesis of lysine through the
RT amino adipate pathway: a key to the evolution of amino acid biosynthesis.";
RL Genome Res. 9:1175-1183(1999).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY, ACTIVITY
RP REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16524361; DOI=10.1042/bj20051711;
RA Jia Y., Tomita T., Yamauchi K., Nishiyama M., Palmer D.R.J.;
RT "Kinetics and product analysis of the reaction catalysed by recombinant
RT homoaconitase from Thermus thermophilus.";
RL Biochem. J. 396:479-485(2006).
CC -!- FUNCTION: Catalyzes the reversible hydration of cis-homoaconitate ((Z)-
CC but-1-ene-1,2,4-tricarboxylate) to homoisocitrate ((1R,2S)-1-
CC hydroxybutane-1,2,4-tricarboxylate). Can catalyze neither the
CC dehydration of (R)-homocitrate ((2R)-2-hydroxybutane-1,2,4-
CC tricarboxylate) into cis-homoaconitate in vitro, nor the reverse
CC reaction. Is not active toward (S)-homocitrate, cis-aconitate or
CC citrate as substrate. {ECO:0000269|PubMed:10613839,
CC ECO:0000269|PubMed:16524361}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-homoisocitrate = cis-homoaconitate + H2O;
CC Xref=Rhea:RHEA:15485, ChEBI:CHEBI:15377, ChEBI:CHEBI:15404,
CC ChEBI:CHEBI:58174; EC=4.2.1.36;
CC Evidence={ECO:0000269|PubMed:16524361};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01027,
CC ECO:0000269|PubMed:16524361};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_01027, ECO:0000269|PubMed:16524361};
CC -!- ACTIVITY REGULATION: Is not inhibited by lysine.
CC {ECO:0000269|PubMed:16524361}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.2 uM for cis-homoaconitate (at 60 degrees Celsius and pH 8)
CC {ECO:0000269|PubMed:16524361};
CC KM=36 uM for homoisocitrate (at 60 degrees Celsius and pH 8)
CC {ECO:0000269|PubMed:16524361};
CC pH dependence:
CC Optimum pH is 8.0. {ECO:0000269|PubMed:16524361};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-alpha-aminoadipate from 2-oxoglutarate: step 3/5.
CC {ECO:0000269|PubMed:10613839}.
CC -!- SUBUNIT: Heterodimer of HacA and HacB. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAS81889.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA33786.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB017109; BAA74762.1; -; mRNA.
DR EMBL; AE017221; AAS81889.1; ALT_INIT; Genomic_DNA.
DR EMBL; AB018379; BAA33786.1; ALT_INIT; Genomic_DNA.
DR PIR; T51171; T51171.
DR RefSeq; WP_041443739.1; NC_005835.1.
DR AlphaFoldDB; Q9ZNE0; -.
DR SMR; Q9ZNE0; -.
DR STRING; 262724.TT_C1547; -.
DR EnsemblBacteria; AAS81889; AAS81889; TT_C1547.
DR KEGG; tth:TT_C1547; -.
DR eggNOG; COG0065; Bacteria.
DR HOGENOM; CLU_006714_3_4_0; -.
DR OMA; GCGPCMG; -.
DR BioCyc; MetaCyc:MON-6723; -.
DR SABIO-RK; Q9ZNE0; -.
DR UniPathway; UPA00033; UER01027.
DR Proteomes; UP000000592; Chromosome.
DR GO; GO:0003861; F:3-isopropylmalate dehydratase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0004409; F:homoaconitate hydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IEA:UniProtKB-UniPathway.
DR CDD; cd01583; IPMI; 1.
DR Gene3D; 3.30.499.10; -; 2.
DR HAMAP; MF_01027; LeuC_type2; 1.
DR InterPro; IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3.
DR InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba.
DR InterPro; IPR018136; Aconitase_4Fe-4S_BS.
DR InterPro; IPR036008; Aconitase_4Fe-4S_dom.
DR InterPro; IPR011826; HAcnase/IPMdehydase_lsu_prok.
DR InterPro; IPR006251; Homoacnase/IPMdehydase_lsu.
DR InterPro; IPR033941; IPMI_cat.
DR Pfam; PF00330; Aconitase; 1.
DR PRINTS; PR00415; ACONITASE.
DR SUPFAM; SSF53732; SSF53732; 1.
DR TIGRFAMs; TIGR01343; hacA_fam; 1.
DR TIGRFAMs; TIGR02086; IPMI_arch; 1.
DR PROSITE; PS00450; ACONITASE_1; 1.
DR PROSITE; PS01244; ACONITASE_2; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Amino-acid biosynthesis; Iron; Iron-sulfur; Lyase;
KW Lysine biosynthesis; Metal-binding.
FT CHAIN 1..418
FT /note="Homoaconitase large subunit"
FT /id="PRO_0000076895"
FT BINDING 292
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01027"
FT BINDING 352
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01027"
FT BINDING 355
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01027"
FT CONFLICT 170..184
FT /note="TAKDAALEMVRLLTA -> HGQGRPPWRWVPLLHRP (in Ref. 3;
FT BAA33786)"
FT /evidence="ECO:0000305"
FT CONFLICT 189..207
FT /note="YMAVEIHLLDGAEALTRGE -> TWRWRSTLRRATLQRGQ (in Ref. 3;
FT BAA33786)"
FT /evidence="ECO:0000305"
FT CONFLICT 211..213
FT /note="LAN -> SQ (in Ref. 3; BAA33786)"
FT /evidence="ECO:0000305"
FT CONFLICT 218..248
FT /note="AGAKAGLVVPSGEILEMYRVPDWLYPDPDAR -> RAKRARVALGRSWRCTG
FT ARLALSRPRCP (in Ref. 3; BAA33786)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 418 AA; 44819 MW; 5B1656899DBB72FC CRC64;
MGQTLAEKIL SHKVGRPVRA GELVVVEVDQ VMVVDSIAGS FFKRLEYLEA TPRYPERVSI
VIDHVAPAAN LEVAKAQKEI REWGKRHGIR VFDVGRGVCH QVLIEEGLAQ PGWVVVGSDS
HSTTYGAVGA FGTGMGATDI ALAAASGRTW LRVPESVKVV FRGRLPKGVT AKDAALEMVR
LLTAEGATYM AVEIHLLDGA EALTRGERMT LANLTVEAGA KAGLVVPSGE ILEMYRVPDW
LYPDPDARYA KEVEIDLSAL TPRVSVPFYV DNVHEVAQVK GKRVDQVFIG TCTNGRIEDL
RAAAEVLRGR KVAPWVRLLV VPASSQVLEE AARDGTLLTL LEAGATIGTP GCGPCMGRHM
GVLAPGEVCV STSNRNFRGR MGAPDAEIYL ASPRVAAASA VAGYLTTPEE LEEEEVHA
