AK_MYCTU
ID AK_MYCTU Reviewed; 421 AA.
AC P9WPX3; L0TGI4; O69676; P0A4Z8; P47731; P97048; P97181;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Aspartokinase;
DE EC=2.7.2.4;
DE AltName: Full=Aspartate kinase;
DE Short=ASK;
GN Name=ask; OrderedLocusNames=Rv3709c; ORFNames=MTV025.057c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RA Gilker J.M., Jucker M.T.;
RT "Mycobacterium tuberculosis ask-alpha, ask-beta and asd genes.";
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS), AND SUBUNIT.
RX PubMed=21393848; DOI=10.1107/s1744309111000030;
RA Schuldt L., Suchowersky R., Veith K., Mueller-Dieckmann J., Weiss M.S.;
RT "Cloning, expression, purification, crystallization and preliminary X-ray
RT diffraction analysis of the regulatory domain of aspartokinase (Rv3709c)
RT from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 67:380-385(2011).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 250-421 IN COMPLEX WITH SUBSTRATE
RP ANALOGS, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=21976064; DOI=10.1007/s13238-011-1094-2;
RA Yang Q., Yu K., Yan L., Li Y., Chen C., Li X.;
RT "Structural view of the regulatory subunit of aspartate kinase from
RT Mycobacterium tuberculosis.";
RL Protein Cell 2:745-754(2011).
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:0000250}.
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 threonine.
CC {ECO:0000269|PubMed:21976064}.
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: Heterotetramer consisting of 2 isoforms Alpha (catalytic and
CC regulation) and of a homodimer of 2 isoforms Beta (regulation).
CC {ECO:0000269|PubMed:21393848, ECO:0000269|PubMed:21976064}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Alpha; Synonyms=Aspartokinase subunit alpha;
CC IsoId=P9WPX3-1; Sequence=Displayed;
CC Name=Beta; Synonyms=Aspartokinase subunit beta;
CC IsoId=P9WPX3-2; Sequence=VSP_018663;
CC -!- SIMILARITY: Belongs to the aspartokinase family. {ECO:0000305}.
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DR EMBL; U90239; AAB49995.1; -; Genomic_DNA.
DR EMBL; U90239; AAB49994.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46535.1; -; Genomic_DNA.
DR PIR; F70794; F70794.
DR RefSeq; NP_218226.1; NC_000962.3. [P9WPX3-1]
DR RefSeq; WP_003419828.1; NZ_NVQJ01000009.1.
DR PDB; 3S1T; X-ray; 1.63 A; A/B=251-421, C=412-421.
DR PDB; 4GO5; X-ray; 2.60 A; X=250-421.
DR PDB; 4GO7; X-ray; 2.00 A; X=250-421.
DR PDBsum; 3S1T; -.
DR PDBsum; 4GO5; -.
DR PDBsum; 4GO7; -.
DR AlphaFoldDB; P9WPX3; -.
DR SMR; P9WPX3; -.
DR STRING; 83332.Rv3709c; -.
DR PaxDb; P9WPX3; -.
DR DNASU; 885223; -.
DR GeneID; 885223; -.
DR KEGG; mtu:Rv3709c; -.
DR TubercuList; Rv3709c; -.
DR eggNOG; COG0527; Bacteria.
DR OMA; DMIVQTI; -.
DR PhylomeDB; P9WPX3; -.
DR BRENDA; 2.7.2.4; 3445.
DR UniPathway; UPA00034; UER00015.
DR UniPathway; UPA00050; UER00461.
DR UniPathway; UPA00051; UER00462.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004072; F:aspartate kinase activity; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IDA:MTBBASE.
DR GO; GO:0009090; P:homoserine biosynthetic process; IBA:GO_Central.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IDA:MTBBASE.
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; 1.
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; Threonine biosynthesis;
KW Transferase.
FT CHAIN 1..421
FT /note="Aspartokinase"
FT /id="PRO_0000002385"
FT DOMAIN 267..348
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 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 BINDING 151..154
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="substrate"
FT /evidence="ECO:0000250"
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
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 292..294
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 298
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 360..361
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 374..375
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 381..382
FT /ligand="substrate"
FT /evidence="ECO:0000250"
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_018663"
FT CONFLICT 288..336
FT /note="DADVNIDMVLQNVSKVEDGKTDITFTCSRDVGPAAVEKLDSLRNEIGFS ->
FT RRRRQHRHGAAERLQGRGRQDRHHLHLLPQTSGPPPWKNWTRSETRSAST (in Ref.
FT 1; AAB49995)"
FT /evidence="ECO:0000305"
FT CONFLICT 383..421
FT /note="IRISVLCRDTELDKAVVALHEAFGLGGDEEATVYAGTGR -> DQRSRCCAA
FT TPNWTRPWSRCMKRSGSAATRRPRCTRGRDGRWACQ (in Ref. 1; AAB49995/
FT AAB49994)"
FT /evidence="ECO:0000305"
FT STRAND 254..261
FT /evidence="ECO:0007829|PDB:3S1T"
FT STRAND 263..275
FT /evidence="ECO:0007829|PDB:3S1T"
FT HELIX 278..288
FT /evidence="ECO:0007829|PDB:3S1T"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:3S1T"
FT TURN 303..305
FT /evidence="ECO:0007829|PDB:3S1T"
FT STRAND 307..315
FT /evidence="ECO:0007829|PDB:3S1T"
FT TURN 316..318
FT /evidence="ECO:0007829|PDB:3S1T"
FT HELIX 319..328
FT /evidence="ECO:0007829|PDB:3S1T"
FT HELIX 330..333
FT /evidence="ECO:0007829|PDB:3S1T"
FT STRAND 336..342
FT /evidence="ECO:0007829|PDB:3S1T"
FT STRAND 344..352
FT /evidence="ECO:0007829|PDB:3S1T"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:4GO5"
FT HELIX 358..370
FT /evidence="ECO:0007829|PDB:3S1T"
FT STRAND 377..381
FT /evidence="ECO:0007829|PDB:3S1T"
FT STRAND 384..390
FT /evidence="ECO:0007829|PDB:3S1T"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:3S1T"
FT HELIX 394..405
FT /evidence="ECO:0007829|PDB:3S1T"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:3S1T"
SQ SEQUENCE 421 AA; 44462 MW; 0567323B0D2085A7 CRC64;
MALVVQKYGG SSVADAERIR RVAERIVATK KQGNDVVVVV SAMGDTTDDL LDLAQQVCPA
PPPRELDMLL TAGERISNAL VAMAIESLGA HARSFTGSQA GVITTGTHGN AKIIDVTPGR
LQTALEEGRV VLVAGFQGVS QDTKDVTTLG RGGSDTTAVA MAAALGADVC EIYTDVDGIF
SADPRIVRNA RKLDTVTFEE MLEMAACGAK VLMLRCVEYA RRHNIPVHVR SSYSDRPGTV
VVGSIKDVPM EDPILTGVAH DRSEAKVTIV GLPDIPGYAA KVFRAVADAD VNIDMVLQNV
SKVEDGKTDI TFTCSRDVGP AAVEKLDSLR NEIGFSQLLY DDHIGKVSLI GAGMRSHPGV
TATFCEALAA VGVNIELIST SEIRISVLCR DTELDKAVVA LHEAFGLGGD EEATVYAGTG
R
