AK_CORGL
ID AK_CORGL Reviewed; 421 AA.
AC P26512; Q59286;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2002, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Aspartokinase;
DE EC=2.7.2.4;
DE AltName: Full=Aspartate kinase;
GN Name=lysC; OrderedLocusNames=Cgl0251, cg0306;
OS Corynebacterium glutamicum (strain ATCC 13032 / DSM 20300 / BCRC 11384 /
OS JCM 1318 / LMG 3730 / NCIMB 10025).
OC Bacteria; Actinobacteria; Corynebacteriales; Corynebacteriaceae;
OC Corynebacterium.
OX NCBI_TaxID=196627;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 13032 / DSM 20300 / BCRC 11384 / JCM 1318 / LMG 3730 / NCIMB
RC 10025;
RX PubMed=1956296; DOI=10.1111/j.1365-2958.1991.tb01893.x;
RA Kalinowski J., Cremer J., Bachmann B., Eggeling L., Sahm H., Puehler A.;
RT "Genetic and biochemical analysis of the aspartokinase from Corynebacterium
RT glutamicum.";
RL Mol. Microbiol. 5:1197-1204(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 13032 / DSM 20300 / BCRC 11384 / JCM 1318 / LMG 3730 / NCIMB
RC 10025;
RX PubMed=12743753; DOI=10.1007/s00253-003-1328-1;
RA Ikeda M., Nakagawa S.;
RT "The Corynebacterium glutamicum genome: features and impacts on
RT biotechnological processes.";
RL Appl. Microbiol. Biotechnol. 62:99-109(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 13032 / DSM 20300 / BCRC 11384 / JCM 1318 / LMG 3730 / NCIMB
RC 10025;
RX PubMed=12948626; DOI=10.1016/s0168-1656(03)00154-8;
RA Kalinowski J., Bathe B., Bartels D., Bischoff N., Bott M., Burkovski A.,
RA Dusch N., Eggeling L., Eikmanns B.J., Gaigalat L., Goesmann A.,
RA Hartmann M., Huthmacher K., Kraemer R., Linke B., McHardy A.C., Meyer F.,
RA Moeckel B., Pfefferle W., Puehler A., Rey D.A., Rueckert C., Rupp O.,
RA Sahm H., Wendisch V.F., Wiegraebe I., Tauch A.;
RT "The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its
RT impact on the production of L-aspartate-derived amino acids and vitamins.";
RL J. Biotechnol. 104:5-25(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-51.
RC STRAIN=ATCC 13032 / DSM 20300 / BCRC 11384 / JCM 1318 / LMG 3730 / NCIMB
RC 10025;
RX PubMed=8117072; DOI=10.1128/aem.60.1.133-140.1994;
RA Patek M., Krumbach K., Eggeling L., Sahm H.;
RT "Leucine synthesis in Corynebacterium glutamicum: enzyme activities,
RT structure of leuA, and effect of leuA inactivation on lysine synthesis.";
RL Appl. Environ. Microbiol. 60:133-140(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 158-421.
RC STRAIN=ATCC 13032 / DSM 20300 / BCRC 11384 / JCM 1318 / LMG 3730 / NCIMB
RC 10025;
RX PubMed=1980002; DOI=10.1007/bf00262424;
RA Kalinowski J., Bachmann B., Thierbach G., Puehler A.;
RT "Aspartokinase genes lysC alpha and lysC beta overlap and are adjacent to
RT the aspartate beta-semialdehyde dehydrogenase gene asd in Corynebacterium
RT glutamicum.";
RL Mol. Gen. Genet. 224:317-324(1990).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 251-421 IN COMPLEX WITH SUBSTRATE
RP ANALOGS, MUTAGENESIS OF GLY-277; ALA-279; GLN-298; SER-301; VAL-360;
RP THR-361; GLU-363 AND PHE-364, ACTIVITY REGULATION, SUBUNIT, AND FUNCTION.
RX PubMed=17350037; DOI=10.1016/j.jmb.2007.02.017;
RA Yoshida A., Tomita T., Kurihara T., Fushinobu S., Kuzuyama T.,
RA Nishiyama M.;
RT "Structural Insight into concerted inhibition of alpha 2 beta 2-type
RT aspartate kinase from Corynebacterium glutamicum.";
RL J. Mol. Biol. 368:521-536(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-421 AND 251-421 AND MUTANT
RP PHE-301 IN COMPLEX WITH SUBSTRATE ANALOGS, FUNCTION, MUTAGENESIS OF
RP SER-301, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=20573952; DOI=10.1074/jbc.m110.111153;
RA Yoshida A., Tomita T., Kuzuyama T., Nishiyama M.;
RT "Mechanism of concerted inhibition of alpha2beta2-type hetero-oligomeric
RT aspartate kinase from Corynebacterium glutamicum.";
RL J. Biol. Chem. 285:27477-27486(2010).
CC -!- FUNCTION: Catalyzes the phosphorylation of the beta-carboxyl group of
CC aspartic acid with ATP to yield 4-phospho-L-aspartate, which is
CC involved in the branched biosynthetic pathway leading to the
CC biosynthesis of amino acids lysine, threonine, isoleucine and
CC methionine. {ECO:0000269|PubMed:17350037, ECO:0000269|PubMed:20573952}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-aspartate = 4-phospho-L-aspartate + ADP;
CC Xref=Rhea:RHEA:23776, ChEBI:CHEBI:29991, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57535, ChEBI:CHEBI:456216; EC=2.7.2.4;
CC -!- ACTIVITY REGULATION: Feedback inhibition by lysine and threonine, but
CC he enzyme is moderately inhibited by lysine alone, and threonine alone
CC has no effect. {ECO:0000269|PubMed:17350037,
CC ECO:0000269|PubMed:20573952}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 1/4.
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-homoserine from L-aspartate: step 1/3.
CC -!- PATHWAY: Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine
CC from L-aspartate: step 1/5.
CC -!- SUBUNIT: Tetramer consisting of 2 isoforms Alpha (catalytic and
CC regulation) and of a homodimer of 2 isoforms Beta (regulation). The
CC dimerization of the beta isoforms is stabilized by the bonding of
CC threonine. {ECO:0000269|PubMed:17350037, ECO:0000269|PubMed:20573952}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Alpha; Synonyms=Aspartokinase subunit alpha;
CC IsoId=P26512-1; Sequence=Displayed;
CC Name=Beta; Synonyms=Aspartokinase subunit beta;
CC IsoId=P26512-2; Sequence=VSP_018659, VSP_018660;
CC -!- SIMILARITY: Belongs to the aspartokinase family. {ECO:0000305}.
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DR EMBL; X57226; CAA40502.1; -; Genomic_DNA.
DR EMBL; X57226; CAA40503.1; -; Genomic_DNA.
DR EMBL; BA000036; BAB97644.1; -; Genomic_DNA.
DR EMBL; BX927148; CAF18822.1; -; Genomic_DNA.
DR EMBL; X70959; CAA50296.1; -; Genomic_DNA.
DR PIR; I40723; I40723.
DR PIR; S15276; S15276.
DR RefSeq; NP_599504.1; NC_003450.3.
DR RefSeq; WP_003855724.1; NC_006958.1.
DR PDB; 2DTJ; X-ray; 1.58 A; A/B=250-421.
DR PDB; 3AAW; X-ray; 2.50 A; A/C=1-421.
DR PDB; 3AB2; X-ray; 2.59 A; A/C/E/G/I/K/M/O=1-421, B/D/F/H/J/L/N/P=251-421.
DR PDB; 3AB4; X-ray; 2.47 A; A/C/E/G/I/K/M/O=1-421, B/D/F/H/J/L/N/P=251-421.
DR PDBsum; 2DTJ; -.
DR PDBsum; 3AAW; -.
DR PDBsum; 3AB2; -.
DR PDBsum; 3AB4; -.
DR AlphaFoldDB; P26512; -.
DR SMR; P26512; -.
DR STRING; 196627.cg0306; -.
DR GeneID; 58310306; -.
DR KEGG; cgb:cg0306; -.
DR KEGG; cgl:Cgl0251; -.
DR PATRIC; fig|196627.13.peg.255; -.
DR eggNOG; COG0527; Bacteria.
DR HOGENOM; CLU_009116_3_2_11; -.
DR OMA; DMIVQTI; -.
DR BioCyc; MetaCyc:MON-6461; -.
DR BioCyc; MetaCyc:MON-6462; -.
DR BRENDA; 2.7.2.4; 960.
DR UniPathway; UPA00034; UER00015.
DR UniPathway; UPA00050; UER00461.
DR UniPathway; UPA00051; UER00462.
DR EvolutionaryTrace; P26512; -.
DR Proteomes; UP000000582; Chromosome.
DR GO; GO:0004072; F:aspartate kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IEA:UniProtKB-UniPathway.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0009088; P:threonine biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd04261; AAK_AKii-LysC-BS; 1.
DR Gene3D; 3.40.1160.10; -; 1.
DR InterPro; IPR036393; AceGlu_kinase-like_sf.
DR InterPro; IPR045865; ACT-like_dom_sf.
DR InterPro; IPR002912; ACT_dom.
DR InterPro; IPR041740; AKii-LysC-BS.
DR InterPro; IPR001048; Asp/Glu/Uridylate_kinase.
DR InterPro; IPR005260; Asp_kin_monofn.
DR InterPro; IPR001341; Asp_kinase.
DR InterPro; IPR018042; Aspartate_kinase_CS.
DR InterPro; IPR027795; CASTOR_ACT_dom.
DR Pfam; PF00696; AA_kinase; 1.
DR Pfam; PF01842; ACT; 1.
DR Pfam; PF13840; ACT_7; 1.
DR PIRSF; PIRSF000726; Asp_kin; 1.
DR SUPFAM; SSF53633; SSF53633; 1.
DR SUPFAM; SSF55021; SSF55021; 2.
DR TIGRFAMs; TIGR00656; asp_kin_monofn; 1.
DR TIGRFAMs; TIGR00657; asp_kinases; 1.
DR PROSITE; PS51671; ACT; 2.
DR PROSITE; PS00324; ASPARTOKINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Amino-acid biosynthesis; ATP-binding;
KW Diaminopimelate biosynthesis; Kinase; Lysine biosynthesis;
KW Nucleotide-binding; Reference proteome; Repeat; Transferase.
FT CHAIN 1..421
FT /note="Aspartokinase"
FT /id="PRO_0000002379"
FT DOMAIN 267..343
FT /note="ACT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT DOMAIN 349..421
FT /note="ACT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT BINDING 7..10
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 25..30
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 45..49
FT /ligand="substrate"
FT BINDING 74
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 125..126
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 151..154
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="substrate"
FT BINDING 174..175
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 180..185
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 210
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 274..279
FT /ligand="substrate"
FT BINDING 274
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 292..294
FT /ligand="substrate"
FT BINDING 298
FT /ligand="substrate"
FT BINDING 360..361
FT /ligand="substrate"
FT BINDING 374..375
FT /ligand="substrate"
FT BINDING 381..382
FT /ligand="substrate"
FT SITE 7
FT /note="Contribution to the catalysis"
FT /evidence="ECO:0000250"
FT SITE 74
FT /note="Contribution to the catalysis"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..249
FT /note="Missing (in isoform Beta)"
FT /evidence="ECO:0000305"
FT /id="VSP_018659"
FT VAR_SEQ 250
FT /note="V -> M (in isoform Beta)"
FT /evidence="ECO:0000305"
FT /id="VSP_018660"
FT MUTAGEN 277
FT /note="G->A: Change in the inhibitory profile upon addition
FT of threonine."
FT /evidence="ECO:0000269|PubMed:17350037"
FT MUTAGEN 279
FT /note="A->V: Absence of inhibition upon addition of
FT threonine and lysine or lysine alone."
FT /evidence="ECO:0000269|PubMed:17350037"
FT MUTAGEN 298
FT /note="Q->A: Change in the inhibitory profile and absence
FT of dimerization upon addition of threonine."
FT /evidence="ECO:0000269|PubMed:17350037"
FT MUTAGEN 301
FT /note="S->F: Absence of inhibition upon addition of
FT threonine and lysine or lysine alone."
FT /evidence="ECO:0000269|PubMed:17350037,
FT ECO:0000269|PubMed:20573952"
FT MUTAGEN 301
FT /note="S->Y: Feedback-resistant and enhanced expression of
FT the asd gene."
FT /evidence="ECO:0000269|PubMed:17350037,
FT ECO:0000269|PubMed:20573952"
FT MUTAGEN 360
FT /note="V->A: Change in the inhibitory profile and shows an
FT different oligomer state upon addition of threonine."
FT /evidence="ECO:0000269|PubMed:17350037"
FT MUTAGEN 361
FT /note="T->A: Change in the inhibitory profile and absence
FT of dimerization upon addition of threonine."
FT /evidence="ECO:0000269|PubMed:17350037"
FT MUTAGEN 363
FT /note="E->A: Change in the inhibitory profile and absence
FT of dimerization upon addition of threonine."
FT /evidence="ECO:0000269|PubMed:17350037"
FT MUTAGEN 364
FT /note="F->A: Change in the inhibitory profile and shows an
FT different oligomer state upon addition of threonine."
FT /evidence="ECO:0000269|PubMed:17350037"
FT CONFLICT 40
FT /note="C -> V (in Ref. 1; CAA40502)"
FT /evidence="ECO:0000305"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:3AB4"
FT HELIX 11..13
FT /evidence="ECO:0007829|PDB:3AB4"
FT HELIX 16..31
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:3AB4"
FT HELIX 46..57
FT /evidence="ECO:0007829|PDB:3AB4"
FT HELIX 63..87
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:3AB4"
FT HELIX 118..126
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 142..150
FT /evidence="ECO:0007829|PDB:3AAW"
FT HELIX 154..165
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 168..175
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:3AB4"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:3AB4"
FT HELIX 198..206
FT /evidence="ECO:0007829|PDB:3AB4"
FT HELIX 214..222
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 227..234
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:3AB4"
FT HELIX 245..247
FT /evidence="ECO:0007829|PDB:3AB4"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:3AB4"
FT STRAND 254..261
FT /evidence="ECO:0007829|PDB:2DTJ"
FT STRAND 263..273
FT /evidence="ECO:0007829|PDB:2DTJ"
FT HELIX 278..288
FT /evidence="ECO:0007829|PDB:2DTJ"
FT STRAND 295..298
FT /evidence="ECO:0007829|PDB:2DTJ"
FT TURN 303..305
FT /evidence="ECO:0007829|PDB:2DTJ"
FT STRAND 307..315
FT /evidence="ECO:0007829|PDB:2DTJ"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:2DTJ"
FT HELIX 319..327
FT /evidence="ECO:0007829|PDB:2DTJ"
FT TURN 328..334
FT /evidence="ECO:0007829|PDB:2DTJ"
FT STRAND 336..342
FT /evidence="ECO:0007829|PDB:2DTJ"
FT STRAND 344..352
FT /evidence="ECO:0007829|PDB:2DTJ"
FT HELIX 358..370
FT /evidence="ECO:0007829|PDB:2DTJ"
FT STRAND 377..381
FT /evidence="ECO:0007829|PDB:2DTJ"
FT STRAND 384..390
FT /evidence="ECO:0007829|PDB:2DTJ"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:2DTJ"
FT HELIX 394..405
FT /evidence="ECO:0007829|PDB:2DTJ"
SQ SEQUENCE 421 AA; 44755 MW; E36B4D0081DE0827 CRC64;
MALVVQKYGG SSLESAERIR NVAERIVATK KAGNDVVVVC SAMGDTTDEL LELAAAVNPV
PPAREMDMLL TAGERISNAL VAMAIESLGA EAQSFTGSQA GVLTTERHGN ARIVDVTPGR
VREALDEGKI CIVAGFQGVN KETRDVTTLG RGGSDTTAVA LAAALNADVC EIYSDVDGVY
TADPRIVPNA QKLEKLSFEE MLELAAVGSK ILVLRSVEYA RAFNVPLRVR SSYSNDPGTL
IAGSMEDIPV EEAVLTGVAT DKSEAKVTVL GISDKPGEAA KVFRALADAE INIDMVLQNV
SSVEDGTTDI TFTCPRSDGR RAMEILKKLQ VQGNWTNVLY DDQVGKVSLV GAGMKSHPGV
TAEFMEALRD VNVNIELIST SEIRISVLIR EDDLDAAARA LHEQFQLGGE DEAVVYAGTG
R
