ID AK_MYCTU Reviewed; 421 AA.
AC P0A4Z8; L0TGI4; O69676; P47731; P97048; P97181;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 01-MAY-2013, entry version 62.
DE RecName: Full=Aspartokinase;
DE EC=2.7.2.4;
DE AltName: Full=Aspartate kinase;
DE Short=ASK;
GN Name=ask; OrderedLocusNames=Rv3709c, MT3812; ORFNames=MTV025.057c;
OS Mycobacterium tuberculosis.
OC Bacteria; Actinobacteria; Actinobacteridae; Actinomycetales;
OC Corynebacterineae; Mycobacteriaceae; Mycobacterium;
OC Mycobacterium tuberculosis complex.
OX NCBI_TaxID=1773;
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.,
RA Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III,
RA Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T.,
RA Connor R., Davies R.M., Devlin K., Feltwell T., Gentles S., Hamlin N.,
RA Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S.,
RA Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A.,
RA Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R.,
RA Sulston J.E., Taylor K., Whitehead S., Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the
RT complete genome sequence.";
RL Nature 393:537-544(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/JB.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H.,
RA Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D.,
RA Salzberg S.L., Delcher A., Utterback T.R., Weidman J.F., Khouri H.M.,
RA Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C.,
RA Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
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.,
RA Weiss M.S.;
RT "Cloning, expression, purification, crystallization and preliminary X-
RT ray diffraction analysis of the regulatory domain of aspartokinase
RT (Rv3709c) 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
RP SUBSTRATE ANALOGS, ENZYME 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
CC of 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 (By similarity).
CC -!- CATALYTIC ACTIVITY: ATP + L-aspartate = ADP + 4-phospho-L-
CC aspartate.
CC -!- ENZYME REGULATION: Feedback inhibition by threonine.
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
CC novo pathway; L-homoserine from L-aspartate: step 1/3.
CC -!- PATHWAY: Amino-acid biosynthesis; L-threonine biosynthesis; L-
CC threonine from L-aspartate: step 1/5.
CC -!- SUBUNIT: Heterotetramer consisting of 2 isoforms Alpha (catalytic
CC and regulation) and of a homodimer of 2 isoforms Beta
CC (regulation).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Alpha; Synonyms=Aspartokinase subunit alpha;
CC IsoId=P0A4Z8-1; Sequence=Displayed;
CC Name=Beta; Synonyms=Aspartokinase subunit beta;
CC IsoId=P0A4Z8-2; Sequence=VSP_018663;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the aspartokinase family.
CC -!- SIMILARITY: Contains 2 ACT domains.
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DR EMBL; U90239; AAB49995.1; -; Genomic_DNA.
DR EMBL; U90239; AAB49994.1; -; Genomic_DNA.
DR EMBL; BX842583; CAA18031.1; -; Genomic_DNA.
DR EMBL; AE000516; AAK48180.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46535.1; -; Genomic_DNA.
DR PIR; F70794; F70794.
DR RefSeq; NP_218226.1; NC_000962.3.
DR RefSeq; NP_338366.1; NC_002755.2.
DR RefSeq; YP_006517201.1; NC_018143.1.
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 ProteinModelPortal; P0A4Z8; -.
DR SMR; P0A4Z8; 1-409.
DR STRING; 83332.Rv3709c; -.
DR PRIDE; P0A4Z8; -.
DR EnsemblBacteria; AAK48180; AAK48180; MT3812.
DR GeneID; 13317323; -.
DR GeneID; 885223; -.
DR GeneID; 926450; -.
DR KEGG; mtc:MT3812; -.
DR KEGG; mtu:Rv3709c; -.
DR KEGG; mtv:RVBD_3709c; -.
DR PATRIC; 18130144; VBIMycTub22151_4164.
DR TubercuList; Rv3709c; -.
DR eggNOG; COG0527; -.
DR HOGENOM; HOG000293093; -.
DR KO; K00928; -.
DR OMA; SVDMIIQ; -.
DR ProtClustDB; PRK06635; -.
DR UniPathway; UPA00034; UER00015.
DR UniPathway; UPA00050; UER00461.
DR UniPathway; UPA00051; UER00462.
DR GO; GO:0005618; C:cell wall; IDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR GO; GO:0016597; F:amino acid binding; IEA:InterPro.
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:0040007; P:growth; IMP:MTBBASE.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IDA:MTBBASE.
DR GO; GO:0009088; P:threonine biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.1160.10; -; 1.
DR InterPro; IPR002912; ACT_dom.
DR InterPro; IPR001048; Asp/Glu/Uridylate_kinase.
DR InterPro; IPR005260; Asp_kin_monofn.
DR InterPro; IPR001341; Asp_kinase_dom.
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; Aa_kinase; 1.
DR TIGRFAMs; TIGR00656; asp_kin_monofn; 1.
DR TIGRFAMs; TIGR00657; asp_kinases; 1.
DR PROSITE; PS00324; ASPARTOKINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Amino-acid biosynthesis;
KW ATP-binding; Complete proteome; Diaminopimelate biosynthesis; Kinase;
KW Lysine biosynthesis; Nucleotide-binding; Reference proteome; Repeat;
KW Threonine biosynthesis; Transferase.
FT CHAIN 1 421 Aspartokinase.
FT /FTId=PRO_0000002385.
FT DOMAIN 266 338 ACT 1.
FT DOMAIN 348 413 ACT 2.
FT REGION 7 10 ATP binding (By similarity).
FT REGION 25 30 Substrate binding.
FT REGION 45 49 Substrate binding.
FT REGION 125 126 Substrate binding.
FT REGION 151 154 Substrate binding (By similarity).
FT REGION 174 175 ATP binding (By similarity).
FT REGION 180 185 ATP binding (By similarity).
FT REGION 292 294 Substrate binding (By similarity).
FT REGION 360 361 Substrate binding (By similarity).
FT REGION 374 375 Substrate binding (By similarity).
FT REGION 381 382 Substrate binding (By similarity).
FT BINDING 41 41 ATP (By similarity).
FT BINDING 74 74 Substrate (By similarity).
FT BINDING 154 154 Substrate (By similarity).
FT BINDING 210 210 ATP (By similarity).
FT BINDING 274 274 Substrate (By similarity).
FT BINDING 298 298 Substrate (By similarity).
FT SITE 7 7 Contribution to the catalysis (By
FT similarity).
FT SITE 74 74 Contribution to the catalysis (By
FT similarity).
FT VAR_SEQ 1 249 Missing (in isoform Beta).
FT /FTId=VSP_018663.
FT CONFLICT 288 336 DADVNIDMVLQNVSKVEDGKTDITFTCSRDVGPAAVEKLDS
FT LRNEIGFS -> RRRRQHRHGAAERLQGRGRQDRHHLHLLP
FT QTSGPPPWKNWTRSETRSAST (in Ref. 1;
FT AAB49995).
FT CONFLICT 383 421 IRISVLCRDTELDKAVVALHEAFGLGGDEEATVYAGTGR
FT -> DQRSRCCAATPNWTRPWSRCMKRSGSAATRRPRCTRGR
FT DGRWACQ (in Ref. 1; AAB49995/AAB49994).
FT STRAND 254 261
FT STRAND 263 273
FT HELIX 278 288
FT STRAND 294 299
FT STRAND 307 315
FT HELIX 316 318
FT HELIX 319 327
FT HELIX 330 333
FT STRAND 336 341
FT STRAND 344 353
FT HELIX 354 356
FT HELIX 358 370
FT STRAND 377 380
FT STRAND 382 390
FT HELIX 391 393
FT HELIX 394 405
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
//
