CYSK_ECOLI
ID CYSK_ECOLI Reviewed; 323 AA.
AC P0ABK5; P11096; P21546;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Cysteine synthase A;
DE Short=CSase A;
DE EC=2.5.1.47;
DE AltName: Full=O-acetylserine (thiol)-lyase A;
DE Short=OAS-TL A;
DE AltName: Full=O-acetylserine sulfhydrylase A;
DE AltName: Full=S-carboxymethylcysteine synthase;
DE EC=4.5.1.5 {ECO:0000269|Ref.6};
DE AltName: Full=Sulfate starvation-induced protein 5;
DE Short=SSI5;
GN Name=cysK; Synonyms=cysZ; OrderedLocusNames=b2414, JW2407;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=3062311; DOI=10.1111/j.1365-2958.1988.tb00089.x;
RA Levy S., Danchin A.;
RT "Phylogeny of metabolic pathways: O-acetylserine sulphydrylase A is
RT homologous to the tryptophan synthase beta subunit.";
RL Mol. Microbiol. 2:777-783(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=3290198; DOI=10.1128/jb.170.7.3150-3157.1988;
RA Byrne C.R., Monroe R.S., Ward K.A., Kredich N.M.;
RT "DNA sequences of the cysK regions of Salmonella typhimurium and
RT Escherichia coli and linkage of the cysK regions to ptsH.";
RL J. Bacteriol. 170:3150-3157(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9205837; DOI=10.1093/dnares/4.2.91;
RA Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T.,
RA Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K.,
RA Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T., Oyama S.,
RA Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H.,
RA Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.;
RT "Construction of a contiguous 874-kb sequence of the Escherichia coli-K12
RT genome corresponding to 50.0-68.8 min on the linkage map and analysis of
RT its sequence features.";
RL DNA Res. 4:91-113(1997).
RN [4]
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 [5]
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 [6]
RP PROTEIN SEQUENCE OF 2-37, FUNCTION AS S-CARBOXYMETHYLCYSTEINE SYNTHASE,
RP CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RA Kumagai H., Suzuki H., Shigematsu H., Tochikura T.;
RT "S-carboxymethylcysteine synthase from Escherichia coli.";
RL Agric. Biol. Chem. 53:2481-2487(1989).
RN [7]
RP PROTEIN SEQUENCE OF 2-13.
RC STRAIN=K12 / EMG2;
RX PubMed=9298646; DOI=10.1002/elps.1150180807;
RA Link A.J., Robison K., Church G.M.;
RT "Comparing the predicted and observed properties of proteins encoded in the
RT genome of Escherichia coli K-12.";
RL Electrophoresis 18:1259-1313(1997).
RN [8]
RP PROTEIN SEQUENCE OF 2-12.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RA Pasquali C., Sanchez J.-C., Ravier F., Golaz O., Hughes G.J., Frutiger S.,
RA Paquet N., Wilkins M., Appel R.D., Bairoch A., Hochstrasser D.F.;
RL Submitted (SEP-1994) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 2-11; 14-19; 36-42; 127-137 AND 236-242.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=8774726; DOI=10.1111/j.1432-1033.1996.0773u.x;
RA Quadroni M., Staudenmann W., Kertesz M.A., James P.;
RT "Analysis of global responses by protein and peptide fingerprinting of
RT proteins isolated by two-dimensional gel electrophoresis. Application to
RT the sulfate-starvation response of Escherichia coli.";
RL Eur. J. Biochem. 239:773-781(1996).
RN [10]
RP PROTEIN SEQUENCE OF 2-9.
RX PubMed=8506346; DOI=10.1073/pnas.90.11.5011;
RA Henzel W.J., Billeci T.M., Stults J.T., Wong S.C., Grimley C., Watanabe C.;
RT "Identifying proteins from two-dimensional gels by molecular mass searching
RT of peptide fragments in protein sequence databases.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5011-5015(1993).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 315-323.
RX PubMed=2457575; DOI=10.1128/jb.170.9.3827-3837.1988;
RA de Reuse H., Danchin A.;
RT "The ptsH, ptsI, and crr genes of the Escherichia coli phosphoenolpyruvate-
RT dependent phosphotransferase system: a complex operon with several modes of
RT transcription.";
RL J. Bacteriol. 170:3827-3837(1988).
RN [12]
RP FUNCTION IN CDI (MICROBIAL INFECTION), INTERACTION WITH CDIA-CT, SUBUNIT
RP (MICROBIAL INFECTION), DISRUPTION PHENOTYPE, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND MUTAGENESIS OF LYS-42.
RC STRAIN=K12 / BW25113, and K12 / X90;
RX PubMed=22333533; DOI=10.1101/gad.182345.111;
RA Diner E.J., Beck C.M., Webb J.S., Low D.A., Hayes C.S.;
RT "Identification of a target cell permissive factor required for contact-
RT dependent growth inhibition (CDI).";
RL Genes Dev. 26:515-525(2012).
RN [13] {ECO:0007744|PDB:5J43, ECO:0007744|PDB:5J5V}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE
RP AND CDIA AND WITH PYRIDOXAL PHOSPHATE; CDIA AND CDII, FUNCTION (MICROBIAL
RP INFECTION), SUBUNIT (MICROBIAL INFECTION), AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / X90;
RX PubMed=27531961; DOI=10.1073/pnas.1607112113;
RA Johnson P.M., Beck C.M., Morse R.P., Garza-Sanchez F., Low D.A.,
RA Hayes C.S., Goulding C.W.;
RT "Unraveling the essential role of CysK in CDI toxin activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:9792-9797(2016).
CC -!- FUNCTION: (Microbial infection) In addition to its role in cysteine
CC synthesis, stimulates the tRNase activity of CdiA-CT from E.coli strain
CC 536 / UPEC; stimulation does not require O-acetylserine sulfhydrylase
CC activity. CdiA is the toxic component of a toxin-immunity protein
CC module, which functions as a cellular contact-dependent growth
CC inhibition (CDI) system. CDI modules allow bacteria to communicate with
CC and inhibit the growth of closely related neighboring bacteria in a
CC contact-dependent fashion (experiments done in strains BW25113 and X90,
CC both K12 derivatives). This protein is not required for CDI of strain
CC EC93, whose toxin may function by forming inner cell membrane pores
CC (PubMed:22333533). CysK stabilizes CdiA-CT, allowing it to bind tRNA
CC substrate; neither CdiA-CT nor CysK bind tRNA alone in vitro
CC (PubMed:27531961). {ECO:0000269|PubMed:22333533,
CC ECO:0000269|PubMed:27531961}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hydrogen sulfide + O-acetyl-L-serine = acetate + L-cysteine;
CC Xref=Rhea:RHEA:14829, ChEBI:CHEBI:29919, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:35235, ChEBI:CHEBI:58340; EC=2.5.1.47;
CC Evidence={ECO:0000269|Ref.6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-chloro-L-alanine + thioglycolate = chloride + H(+) + S-
CC carboxymethyl-L-cysteine; Xref=Rhea:RHEA:22868, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17996, ChEBI:CHEBI:30066, ChEBI:CHEBI:57662,
CC ChEBI:CHEBI:58132; EC=4.5.1.5; Evidence={ECO:0000269|Ref.6};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:27531961, ECO:0000269|Ref.6};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40 mM for 3-chloro-L-alanine {ECO:0000269|Ref.6};
CC KM=15.4 mM for thioglycolate {ECO:0000269|Ref.6};
CC pH dependence:
CC Optimum pH is 9-10.5. {ECO:0000269|Ref.6};
CC Temperature dependence:
CC Optimum temperature is 50 degrees Celsius. {ECO:0000269|Ref.6};
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine
CC from L-serine: step 2/2.
CC -!- SUBUNIT: Homodimer (Ref.6, PubMed:27531961). Forms a cysteine synthase
CC complex with 1 copy of CysE (By similarity).
CC {ECO:0000250|UniProtKB:P0A1E3, ECO:0000269|PubMed:22333533,
CC ECO:0000269|PubMed:27531961, ECO:0000269|Ref.6}.
CC -!- SUBUNIT: (Microbial infection) Interacts with CdiA-CT from strain 536 /
CC UPEC, this is blocked upon preincubation with O-acetyl-L-serine. CysK
CC forms a complex with CdiA-CT/CdiI (PubMed:22333533). One CdiA toxin
CC subunit binds to each subunit of the CysK homodimer, and one CdiI
CC immunity protein binds to each toxin subunit; the immune complex is
CC thus a dimer of trimers. The 4 C-terminal residues of CdiA fit into the
CC active site of CysK (PubMed:27531961). {ECO:0000269|PubMed:22333533,
CC ECO:0000269|PubMed:27531961}.
CC -!- INTERACTION:
CC P0ABK5; P0A9D4: cysE; NbExp=4; IntAct=EBI-553933, EBI-1133237;
CC P0ABK5; P0ABK5: cysK; NbExp=2; IntAct=EBI-553933, EBI-553933;
CC -!- INDUCTION: Repressed by sulfate or cysteine.
CC -!- DISRUPTION PHENOTYPE: Significant decrease in tRNA nuclease activity of
CC contact-dependent growth inhibitor CdiA-CT from strain 536 / UPEC
CC (deletion in strain BW25113). {ECO:0000269|PubMed:22333533,
CC ECO:0000269|PubMed:27531961}.
CC -!- SIMILARITY: Belongs to the cysteine synthase/cystathionine beta-
CC synthase family. {ECO:0000305}.
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DR EMBL; X12615; CAA31137.1; -; Genomic_DNA.
DR EMBL; M21451; AAA23654.1; -; Genomic_DNA.
DR EMBL; U00096; AAC75467.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA16288.1; -; Genomic_DNA.
DR EMBL; M21994; AAA24383.1; -; Genomic_DNA.
DR PIR; E65015; SYECAC.
DR RefSeq; NP_416909.1; NC_000913.3.
DR RefSeq; WP_000034402.1; NZ_STEB01000039.1.
DR PDB; 5J43; X-ray; 2.70 A; A/E=1-323.
DR PDB; 5J5V; X-ray; 2.75 A; A/D=1-323.
DR PDBsum; 5J43; -.
DR PDBsum; 5J5V; -.
DR AlphaFoldDB; P0ABK5; -.
DR SASBDB; P0ABK5; -.
DR SMR; P0ABK5; -.
DR BioGRID; 4259701; 23.
DR BioGRID; 851217; 1.
DR ComplexPortal; CPX-3742; cysEK cysteine synthase complex.
DR DIP; DIP-36170N; -.
DR IntAct; P0ABK5; 14.
DR STRING; 511145.b2414; -.
DR SWISS-2DPAGE; P0ABK5; -.
DR jPOST; P0ABK5; -.
DR PaxDb; P0ABK5; -.
DR PRIDE; P0ABK5; -.
DR EnsemblBacteria; AAC75467; AAC75467; b2414.
DR EnsemblBacteria; BAA16288; BAA16288; BAA16288.
DR GeneID; 67416814; -.
DR GeneID; 946877; -.
DR KEGG; ecj:JW2407; -.
DR KEGG; eco:b2414; -.
DR PATRIC; fig|1411691.4.peg.4317; -.
DR EchoBASE; EB0189; -.
DR eggNOG; COG0031; Bacteria.
DR InParanoid; P0ABK5; -.
DR OMA; FWDSGER; -.
DR PhylomeDB; P0ABK5; -.
DR BioCyc; EcoCyc:ACSERLYA-MON; -.
DR BioCyc; MetaCyc:ACSERLYA-MON; -.
DR BRENDA; 2.5.1.47; 2026.
DR SABIO-RK; P0ABK5; -.
DR UniPathway; UPA00136; UER00200.
DR PRO; PR:P0ABK5; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0009333; C:cysteine synthase complex; IDA:EcoCyc.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0004124; F:cysteine synthase activity; IDA:EcoliWiki.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0080146; F:L-cysteine desulfhydrase activity; IMP:EcoCyc.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:EcoCyc.
DR GO; GO:0050272; F:S-carboxymethylcysteine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0016740; F:transferase activity; IDA:EcoliWiki.
DR GO; GO:0008652; P:cellular amino acid biosynthetic process; IDA:EcoliWiki.
DR GO; GO:0019344; P:cysteine biosynthetic process; IBA:GO_Central.
DR GO; GO:0006535; P:cysteine biosynthetic process from serine; IDA:ComplexPortal.
DR Gene3D; 3.40.50.1100; -; 2.
DR InterPro; IPR005856; Cys_synth.
DR InterPro; IPR005859; CysK.
DR InterPro; IPR001216; P-phosphate_BS.
DR InterPro; IPR001926; PLP-dep.
DR InterPro; IPR036052; Trypto_synt_PLP_dependent.
DR Pfam; PF00291; PALP; 1.
DR SUPFAM; SSF53686; SSF53686; 1.
DR TIGRFAMs; TIGR01139; cysK; 1.
DR TIGRFAMs; TIGR01136; cysKM; 1.
DR PROSITE; PS00901; CYS_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Amino-acid biosynthesis;
KW Cysteine biosynthesis; Direct protein sequencing; Lyase;
KW Pyridoxal phosphate; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8506346,
FT ECO:0000269|PubMed:8774726, ECO:0000269|PubMed:9298646,
FT ECO:0000269|Ref.6, ECO:0000269|Ref.8"
FT CHAIN 2..323
FT /note="Cysteine synthase A"
FT /id="PRO_0000167086"
FT BINDING 8
FT /ligand="hydrogen sulfide"
FT /ligand_id="ChEBI:CHEBI:29919"
FT /ligand_note="allosteric inhibitor; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P0A1E3"
FT BINDING 35
FT /ligand="hydrogen sulfide"
FT /ligand_id="ChEBI:CHEBI:29919"
FT /ligand_note="allosteric inhibitor; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A1E3"
FT BINDING 72
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250"
FT BINDING 177..181
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250"
FT BINDING 269
FT /ligand="hydrogen sulfide"
FT /ligand_id="ChEBI:CHEBI:29919"
FT /ligand_note="allosteric inhibitor; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A1E3"
FT BINDING 273
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250"
FT MOD_RES 42
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:27531961"
FT MUTAGEN 42
FT /note="K->A: Still stimulates tRNase activity of CdiA-CT in
FT vitro and in vivo."
FT /evidence="ECO:0000269|PubMed:22333533"
FT CONFLICT 182
FT /note="L -> W (in Ref. 2; AAA23654)"
FT /evidence="ECO:0000305"
FT CONFLICT 186..187
FT /note="SR -> TP (in Ref. 2; AAA23654)"
FT /evidence="ECO:0000305"
FT STRAND 5..7
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 8..11
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 28..32
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 44..55
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 72..83
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 98..106
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 119..133
FT /evidence="ECO:0007829|PDB:5J43"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:5J43"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 148..155
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 157..165
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 180..189
FT /evidence="ECO:0007829|PDB:5J43"
FT TURN 190..192
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 210..215
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:5J43"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 252..266
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 272..284
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:5J5V"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:5J43"
FT HELIX 303..306
FT /evidence="ECO:0007829|PDB:5J43"
SQ SEQUENCE 323 AA; 34490 MW; 20ADDE911845AE72 CRC64;
MSKIFEDNSL TIGHTPLVRL NRIGNGRILA KVESRNPSFS VKCRIGANMI WDAEKRGVLK
PGVELVEPTS GNTGIALAYV AAARGYKLTL TMPETMSIER RKLLKALGAN LVLTEGAKGM
KGAIQKAEEI VASNPEKYLL LQQFSNPANP EIHEKTTGPE IWEDTDGQVD VFIAGVGTGG
TLTGVSRYIK GTKGKTDLIS VAVEPTDSPV IAQALAGEEI KPGPHKIQGI GAGFIPANLD
LKLVDKVIGI TNEEAISTAR RLMEEEGILA GISSGAAVAA ALKLQEDESF TNKNIVVILP
SSGERYLSTA LFADLFTEKE LQQ
