AK3_ECOLI
ID AK3_ECOLI Reviewed; 449 AA.
AC P08660; Q2M6T0;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Lysine-sensitive aspartokinase 3;
DE EC=2.7.2.4 {ECO:0000269|PubMed:14623187};
DE AltName: Full=Aspartate kinase III;
DE Short=AKIII;
DE AltName: Full=Lysine-sensitive aspartokinase III;
GN Name=lysC; Synonyms=apk; OrderedLocusNames=b4024, JW3984;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-27.
RC STRAIN=K12;
RX PubMed=3003049; DOI=10.1016/s0021-9258(17)36051-9;
RA Cassan M., Parsot C., Cohen G.N., Patte J.-C.;
RT "Nucleotide sequence of lysC gene encoding the lysine-sensitive
RT aspartokinase III of Escherichia coli K12. Evolutionary pathway leading to
RT three isofunctional enzymes.";
RL J. Biol. Chem. 261:1052-1057(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=8265357; DOI=10.1093/nar/21.23.5408;
RA Blattner F.R., Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L.;
RT "Analysis of the Escherichia coli genome. IV. DNA sequence of the region
RT from 89.2 to 92.8 minutes.";
RL Nucleic Acids Res. 21:5408-5417(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
RX PubMed=6312411; DOI=10.1093/nar/11.18.6157;
RA Cassan M., Ronceray J., Patte J.-C.;
RT "Nucleotide sequence of the promoter region of the E. coli lysC gene.";
RL Nucleic Acids Res. 11:6157-6166(1983).
RN [6]
RP SUBUNIT, INVOLVEMENT OF C-TERMINUS IN DIMERIZATION, MUTAGENESIS OF LYS-8;
RP GLU-119; ARG-198 AND ASP-202, AND CATALYTIC ACTIVITY.
RX PubMed=14623187; DOI=10.1016/j.jmb.2003.09.038;
RA Marco-Marin C., Ramon-Maiques S., Tavarez S., Rubio V.;
RT "Site-directed mutagenesis of Escherichia coli acetylglutamate kinase and
RT aspartokinase III probes the catalytic and substrate-binding mechanisms of
RT these amino acid kinase family enzymes and allows three-dimensional
RT modelling of aspartokinase.";
RL J. Mol. Biol. 334:459-476(2003).
RN [7] {ECO:0007744|PDB:2J0W, ECO:0007744|PDB:2J0X}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEXES WITH ADP; ASPARTATE AND
RP LYSINE INHIBITOR, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=16905770; DOI=10.1074/jbc.m605886200;
RA Kotaka M., Ren J., Lockyer M., Hawkins A.R., Stammers D.K.;
RT "Structures of R- and T-state Escherichia coli aspartokinase III.
RT Mechanisms of the allosteric transition and inhibition by lysine.";
RL J. Biol. Chem. 281:31544-31552(2006).
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 Evidence={ECO:0000269|PubMed:14623187};
CC -!- ACTIVITY REGULATION: Synthesis and activity are sensitive to the
CC allosteric inhibitor lysine, one of the end metabolites of the aspartic
CC acid family branched pathway. {ECO:0000269|PubMed:16905770}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 1/4.
CC -!- SUBUNIT: Homodimer. In the inactive form a homotetramer is formed.
CC {ECO:0000269|PubMed:14623187, ECO:0000269|PubMed:16905770}.
CC -!- MISCELLANEOUS: Aspartokinases I and II also catalyze the same
CC reaction(s).
CC -!- SIMILARITY: Belongs to the aspartokinase family. {ECO:0000305}.
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DR EMBL; M11812; AAA24095.1; -; Genomic_DNA.
DR EMBL; U00006; AAC43118.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76994.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE78026.1; -; Genomic_DNA.
DR EMBL; X00008; CAA24910.1; -; Genomic_DNA.
DR PIR; G65209; KIECD3.
DR RefSeq; NP_418448.1; NC_000913.3.
DR RefSeq; WP_001290310.1; NZ_SSZK01000049.1.
DR PDB; 2J0W; X-ray; 2.50 A; A=1-449.
DR PDB; 2J0X; X-ray; 2.80 A; A/B=1-449.
DR PDBsum; 2J0W; -.
DR PDBsum; 2J0X; -.
DR AlphaFoldDB; P08660; -.
DR PCDDB; P08660; -.
DR SMR; P08660; -.
DR BioGRID; 4261955; 8.
DR STRING; 511145.b4024; -.
DR jPOST; P08660; -.
DR PaxDb; P08660; -.
DR PRIDE; P08660; -.
DR DNASU; 948531; -.
DR EnsemblBacteria; AAC76994; AAC76994; b4024.
DR EnsemblBacteria; BAE78026; BAE78026; BAE78026.
DR GeneID; 948531; -.
DR KEGG; ecj:JW3984; -.
DR KEGG; eco:b4024; -.
DR PATRIC; fig|1411691.4.peg.2689; -.
DR EchoBASE; EB0545; -.
DR eggNOG; COG0527; Bacteria.
DR HOGENOM; CLU_009116_6_0_6; -.
DR InParanoid; P08660; -.
DR OMA; LMSCGEV; -.
DR PhylomeDB; P08660; -.
DR BioCyc; EcoCyc:ASPKINIII-MON; -.
DR BioCyc; MetaCyc:ASPKINIII-MON; -.
DR BRENDA; 2.7.2.4; 2026.
DR SABIO-RK; P08660; -.
DR UniPathway; UPA00034; UER00015.
DR EvolutionaryTrace; P08660; -.
DR PRO; PR:P08660; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0004072; F:aspartate kinase activity; IDA:EcoCyc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009090; P:homoserine biosynthetic process; IDA:EcoCyc.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IDA:EcoCyc.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR CDD; cd04258; AAK_AKiii-LysC-EC; 1.
DR Gene3D; 1.20.120.1320; -; 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; IPR041745; AKiii-LysC-EC.
DR InterPro; IPR001048; Asp/Glu/Uridylate_kinase.
DR InterPro; IPR005260; Asp_kin_monofn.
DR InterPro; IPR001341; Asp_kinase.
DR InterPro; IPR042199; AsparK_Bifunc_asparK/hSer_DH.
DR InterPro; IPR018042; Aspartate_kinase_CS.
DR Pfam; PF00696; AA_kinase; 1.
DR Pfam; PF01842; ACT; 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; 1.
DR PROSITE; PS00324; ASPARTOKINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Amino-acid biosynthesis; ATP-binding;
KW Direct protein sequencing; Kinase; Lysine biosynthesis; Nucleotide-binding;
KW Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..449
FT /note="Lysine-sensitive aspartokinase 3"
FT /id="PRO_0000066676"
FT DOMAIN 313..394
FT /note="ACT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT REGION 2..245
FT /note="Aspartokinase"
FT REGION 246..449
FT /note="Interface"
FT REGION 299..449
FT /note="Required for homodimerization"
FT BINDING 8..11
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 45
FT /ligand="substrate"
FT BINDING 119
FT /ligand="substrate"
FT BINDING 198..201
FT /ligand="substrate"
FT BINDING 221..222
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 227
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 257..258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 318
FT /ligand="L-lysine"
FT /ligand_id="ChEBI:CHEBI:32551"
FT /ligand_note="allosteric inhibitor; ligand shared between
FT homodimeric partners"
FT /evidence="ECO:0007744|PDB:2J0X"
FT BINDING 321
FT /ligand="L-lysine"
FT /ligand_id="ChEBI:CHEBI:32551"
FT /ligand_note="allosteric inhibitor; ligand shared between
FT homodimeric partners"
FT /evidence="ECO:0007744|PDB:2J0X"
FT BINDING 324..325
FT /ligand="L-lysine"
FT /ligand_id="ChEBI:CHEBI:32551"
FT /ligand_note="allosteric inhibitor; ligand shared between
FT homodimeric partners"
FT /evidence="ECO:0007744|PDB:2J0X"
FT BINDING 338..340
FT /ligand="L-lysine"
FT /ligand_id="ChEBI:CHEBI:32551"
FT /ligand_note="allosteric inhibitor; ligand shared between
FT homodimeric partners"
FT /evidence="ECO:0007744|PDB:2J0X"
FT BINDING 345..346
FT /ligand="L-lysine"
FT /ligand_id="ChEBI:CHEBI:32551"
FT /ligand_note="allosteric inhibitor; ligand shared between
FT homodimeric partners"
FT /evidence="ECO:0007744|PDB:2J0X"
FT MUTAGEN 8
FT /note="K->R: Reduces activity about 98%. Increases KM for
FT aspartate about 40-fold, enzyme is less sensitive to lysine
FT inhibition."
FT /evidence="ECO:0000269|PubMed:14623187"
FT MUTAGEN 119
FT /note="E->D: Increases KM for aspartate about 3000-fold."
FT /evidence="ECO:0000269|PubMed:14623187"
FT MUTAGEN 198
FT /note="R->K: Increases KM for aspartate about 200-fold."
FT /evidence="ECO:0000269|PubMed:14623187"
FT MUTAGEN 202
FT /note="D->E: Reduces activity about 98%. Increases KM for
FT aspartate about 40-fold, enzyme is less sensitive to lysine
FT inhibition."
FT /evidence="ECO:0000269|PubMed:14623187"
FT CONFLICT 14..15
FT /note="VA -> AS (in Ref. 5; CAA24910)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="M -> E (in Ref. 5; CAA24910)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="G -> C (in Ref. 1; AAA24095)"
FT /evidence="ECO:0000305"
FT CONFLICT 401
FT /note="G -> A (in Ref. 1; AAA24095)"
FT /evidence="ECO:0000305"
FT STRAND 5..9
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 17..27
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 44..51
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 57..75
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 82..102
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 108..131
FT /evidence="ECO:0007829|PDB:2J0W"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:2J0X"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 159..169
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 171..176
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 177..187
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 200..211
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 215..229
FT /evidence="ECO:0007829|PDB:2J0W"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 245..253
FT /evidence="ECO:0007829|PDB:2J0W"
FT TURN 261..263
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 264..270
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 274..280
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:2J0X"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 298..313
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:2J0X"
FT HELIX 321..328
FT /evidence="ECO:0007829|PDB:2J0W"
FT TURN 329..336
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 340..345
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 348..353
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 368..377
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 380..395
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 402..407
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 408..410
FT /evidence="ECO:0007829|PDB:2J0X"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:2J0W"
FT STRAND 426..432
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:2J0W"
FT HELIX 436..448
FT /evidence="ECO:0007829|PDB:2J0W"
SQ SEQUENCE 449 AA; 48532 MW; 5B41CE3A6E4D984B CRC64;
MSEIVVSKFG GTSVADFDAM NRSADIVLSD ANVRLVVLSA SAGITNLLVA LAEGLEPGER
FEKLDAIRNI QFAILERLRY PNVIREEIER LLENITVLAE AAALATSPAL TDELVSHGEL
MSTLLFVEIL RERDVQAQWF DVRKVMRTND RFGRAEPDIA ALAELAALQL LPRLNEGLVI
TQGFIGSENK GRTTTLGRGG SDYTAALLAE ALHASRVDIW TDVPGIYTTD PRVVSAAKRI
DEIAFAEAAE MATFGAKVLH PATLLPAVRS DIPVFVGSSK DPRAGGTLVC NKTENPPLFR
ALALRRNQTL LTLHSLNMLH SRGFLAEVFG ILARHNISVD LITTSEVSVA LTLDTTGSTS
TGDTLLTQSL LMELSALCRV EVEEGLALVA LIGNDLSKAC GVGKEVFGVL EPFNIRMICY
GASSHNLCFL VPGEDAEQVV QKLHSNLFE
