METC_ECOLI
ID METC_ECOLI Reviewed; 395 AA.
AC P06721; Q2M9J1;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Cystathionine beta-lyase MetC {ECO:0000303|PubMed:8831789};
DE Short=CBL {ECO:0000303|PubMed:8831789};
DE Short=CL {ECO:0000303|PubMed:8566238};
DE EC=4.4.1.13 {ECO:0000269|PubMed:7049234};
DE AltName: Full=Beta-cystathionase MetC {ECO:0000303|PubMed:3513164};
DE AltName: Full=Cysteine desulfhydrase MetC {ECO:0000303|PubMed:12883870};
DE Short=CD {ECO:0000303|PubMed:12883870};
DE EC=4.4.1.28 {ECO:0000269|PubMed:12883870};
DE AltName: Full=Cysteine lyase MetC;
DE AltName: Full=Cysteine-S-conjugate beta-lyase MetC;
GN Name=metC {ECO:0000303|PubMed:3513164}; OrderedLocusNames=b3008, JW2975;
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 2-11.
RC STRAIN=K12;
RX PubMed=3513164; DOI=10.1073/pnas.83.4.867;
RA Belfaiza J., Parsot C., Martel A., de la Tour C.B., Margarita D.,
RA Cohen G.N., Saint-Girons I.;
RT "Evolution in biosynthetic pathways: two enzymes catalyzing consecutive
RT steps in methionine biosynthesis originate from a common ancestor and
RT possess a similar regulatory region.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:867-871(1986).
RN [2]
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 [3]
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 [4]
RP PROTEIN SEQUENCE OF 194-221, COFACTOR, AND PYRIDOXAL PHOSPHATE AT LYS-210.
RX PubMed=3307782; DOI=10.1016/0006-291x(87)90968-5;
RA Martel A., Bouthier de la Tour C., Le Goffic F.;
RT "Pyridoxal 5'phosphate binding site of Escherichia coli beta cystathionase
RT and cystathionine gamma synthase comparison of their sequences.";
RL Biochem. Biophys. Res. Commun. 147:565-571(1987).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=7049234; DOI=10.1021/bi00256a005;
RA Dwivedi C.M., Ragin R.C., Uren J.R.;
RT "Cloning, purification, and characterization of beta-cystathionase from
RT Escherichia coli.";
RL Biochemistry 21:3064-3069(1982).
RN [6]
RP COFACTOR, AND CRYSTALLIZATION.
RX PubMed=8566238; DOI=10.1016/0014-5793(95)01499-3;
RA Laber B., Clausen T., Huber R., Messerschmidt A., Egner U.,
RA Mueller-Fahrnow A., Pohlenz H.D.;
RT "Cloning, purification, and crystallization of Escherichia coli
RT cystathionine beta-lyase.";
RL FEBS Lett. 379:94-96(1996).
RN [7]
RP IDENTIFICATION BY 2D-GEL.
RX PubMed=9298644; DOI=10.1002/elps.1150180805;
RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.;
RT "Escherichia coli proteome analysis using the gene-protein database.";
RL Electrophoresis 18:1243-1251(1997).
RN [8]
RP FUNCTION AS A CYSTEINE DESULFHYDRASE, AND CATALYTIC ACTIVITY.
RX PubMed=12883870; DOI=10.1007/s00253-003-1262-2;
RA Awano N., Wada M., Kohdoh A., Oikawa T., Takagi H., Nakamori S.;
RT "Effect of cysteine desulfhydrase gene disruption on L-cysteine
RT overproduction in Escherichia coli.";
RL Appl. Microbiol. Biotechnol. 62:239-243(2003).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=16000837; DOI=10.1128/aem.71.7.4149-4152.2005;
RA Awano N., Wada M., Mori H., Nakamori S., Takagi H.;
RT "Identification and functional analysis of Escherichia coli cysteine
RT desulfhydrases.";
RL Appl. Environ. Microbiol. 71:4149-4152(2005).
RN [10]
RP FUNCTION AS AN ALANINE RACEMASE.
RX PubMed=21193606; DOI=10.1128/jb.01027-10;
RA Kang L., Shaw A.C., Xu D., Xia W., Zhang J., Deng J., Woeldike H.F.,
RA Liu Y., Su J.;
RT "Upregulation of MetC is essential for D-alanine-independent growth of an
RT alr/dadX-deficient Escherichia coli strain.";
RL J. Bacteriol. 193:1098-1106(2011).
RN [11] {ECO:0007744|PDB:1CL1}
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS), SUBUNIT, AND PYRIDOXAL PHOSPHATE AT
RP LYS-210.
RX PubMed=8831789; DOI=10.1006/jmbi.1996.0508;
RA Clausen T., Huber R., Laber B., Pohlenz H.-D., Messerschmidt A.;
RT "Crystal structure of the pyridoxal-5'-phosphate dependent cystathionine
RT beta-lyase from Escherichia coli at 1.83 A.";
RL J. Mol. Biol. 262:202-224(1996).
RN [12] {ECO:0007744|PDB:1CL2}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH
RP AMINOETHOXYVINYLGLYCINE, AND ACTIVITY REGULATION.
RX PubMed=9376370; DOI=10.1021/bi970630m;
RA Clausen T., Huber R., Messerschmidt A., Pohlenz H.D., Laber B.;
RT "Slow-binding inhibition of Escherichia coli cystathionine beta-lyase by L-
RT aminoethoxyvinylglycine: a kinetic and X-ray study.";
RL Biochemistry 36:12633-12643(1997).
RN [13] {ECO:0007744|PDB:2FQ6, ECO:0007744|PDB:2GQN}
RP X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) IN COMPLEXES WITH INHIBITORS.
RX PubMed=17300162; DOI=10.1021/jm061132r;
RA Ejim L.J., Blanchard J.E., Koteva K.P., Sumerfield R., Elowe N.H.,
RA Chechetto J.D., Brown E.D., Junop M.S., Wright G.D.;
RT "Inhibitors of bacterial cystathionine beta-lyase: leads for new
RT antimicrobial agents and probes of enzyme structure and function.";
RL J. Med. Chem. 50:755-764(2007).
RN [14] {ECO:0007744|PDB:4ITG}
RP X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF MUTANT SER-113.
RA Soo V.W.C., Yosaatmadja Y., Squire C.J., Patrick W.M.;
RT "E. coli cystathionine beta-lyase (MetC) P113S mutant.";
RL Submitted (JAN-2013) to the PDB data bank.
RN [15] {ECO:0007744|PDB:4ITX}
RP X-RAY CRYSTALLOGRAPHY (1.61 ANGSTROMS) OF MUTANT SER-113.
RA Soo V.W.C., Yosaatmadja Y., Squire C.J., Patrick W.M.;
RT "Structure and activity of P113S mutant of E. coli Cystathionine beta-lyase
RT (MetC).";
RL Submitted (JAN-2013) to the PDB data bank.
CC -!- FUNCTION: Primarily catalyzes the cleavage of cystathionine to
CC homocysteine, pyruvate and ammonia during methionine biosynthesis
CC (PubMed:7049234). Also exhibits cysteine desulfhydrase activity,
CC producing sulfide from cysteine (PubMed:12883870). In addition, under
CC certain growth conditions, exhibits significant alanine racemase
CC coactivity (PubMed:21193606). {ECO:0000269|PubMed:12883870,
CC ECO:0000269|PubMed:21193606, ECO:0000269|PubMed:7049234}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L,L-cystathionine = L-homocysteine + NH4(+) + pyruvate;
CC Xref=Rhea:RHEA:13965, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:58161, ChEBI:CHEBI:58199;
CC Evidence={ECO:0000269|PubMed:7049234};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-cysteine = H(+) + hydrogen sulfide + NH4(+) +
CC pyruvate; Xref=Rhea:RHEA:24931, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:29919,
CC ChEBI:CHEBI:35235; EC=4.4.1.28;
CC Evidence={ECO:0000269|PubMed:12883870};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an S-substituted L-cysteine + H2O = a thiol + NH4(+) +
CC pyruvate; Xref=Rhea:RHEA:18121, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:29256, ChEBI:CHEBI:58717; EC=4.4.1.13;
CC Evidence={ECO:0000269|PubMed:7049234};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:3307782, ECO:0000269|PubMed:7049234,
CC ECO:0000269|PubMed:8566238};
CC -!- ACTIVITY REGULATION: L-cysteine inhibits cystathionine beta-lyase
CC activity competitively (PubMed:7049234). Inhibited by
CC aminoethoxyvinylglycine (AVG) (PubMed:9376370).
CC {ECO:0000269|PubMed:7049234, ECO:0000269|PubMed:9376370}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.04 mM for L-cystathionine {ECO:0000269|PubMed:7049234};
CC KM=0.25 mM for L-cystine {ECO:0000269|PubMed:7049234};
CC Vmax=249 umol/min/mg enzyme with L-cystathionine as substrate
CC {ECO:0000269|PubMed:7049234};
CC Vmax=263 umol/min/mg enzyme with L-cystine as substrate
CC {ECO:0000269|PubMed:7049234};
CC pH dependence:
CC Optimum pH is 8.0-9.0. {ECO:0000269|PubMed:7049234};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-homocysteine from L-cystathionine: step 1/1. {ECO:0000305}.
CC -!- SUBUNIT: Homotetramer; dimer of dimers. {ECO:0000269|PubMed:8831789}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the gene increases the amounts of
CC L-cysteine and L-cystine produced after 72 hours of cultivation.
CC {ECO:0000269|PubMed:16000837}.
CC -!- SIMILARITY: Belongs to the trans-sulfuration enzymes family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA69175.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M12858; AAA24158.1; -; Genomic_DNA.
DR EMBL; U28377; AAA69175.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAC76044.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77065.1; -; Genomic_DNA.
DR PIR; A25153; WZECCB.
DR RefSeq; NP_417481.1; NC_000913.3.
DR RefSeq; WP_001301079.1; NZ_SSZK01000023.1.
DR PDB; 1CL1; X-ray; 1.83 A; A/B=1-395.
DR PDB; 1CL2; X-ray; 2.20 A; A/B=1-395.
DR PDB; 2FQ6; X-ray; 1.78 A; A/B=1-395.
DR PDB; 2GQN; X-ray; 1.80 A; A/B=1-395.
DR PDB; 4ITG; X-ray; 1.74 A; A/B=1-395.
DR PDB; 4ITX; X-ray; 1.61 A; A/B=1-395.
DR PDBsum; 1CL1; -.
DR PDBsum; 1CL2; -.
DR PDBsum; 2FQ6; -.
DR PDBsum; 2GQN; -.
DR PDBsum; 4ITG; -.
DR PDBsum; 4ITX; -.
DR AlphaFoldDB; P06721; -.
DR SMR; P06721; -.
DR BioGRID; 4261419; 41.
DR DIP; DIP-10193N; -.
DR IntAct; P06721; 6.
DR STRING; 511145.b3008; -.
DR BindingDB; P06721; -.
DR ChEMBL; CHEMBL1075079; -.
DR jPOST; P06721; -.
DR PaxDb; P06721; -.
DR PRIDE; P06721; -.
DR EnsemblBacteria; AAC76044; AAC76044; b3008.
DR EnsemblBacteria; BAE77065; BAE77065; BAE77065.
DR GeneID; 946240; -.
DR KEGG; ecj:JW2975; -.
DR KEGG; eco:b3008; -.
DR PATRIC; fig|511145.12.peg.3102; -.
DR EchoBASE; EB0578; -.
DR eggNOG; COG0626; Bacteria.
DR HOGENOM; CLU_018986_5_1_6; -.
DR InParanoid; P06721; -.
DR OMA; GPYTYGR; -.
DR PhylomeDB; P06721; -.
DR BioCyc; EcoCyc:CYSTATHIONINE-BETA-LYASE-MON; -.
DR BioCyc; MetaCyc:CYSTATHIONINE-BETA-LYASE-MON; -.
DR BRENDA; 4.4.1.13; 2026.
DR BRENDA; 5.1.1.1; 2026.
DR UniPathway; UPA00051; UER00078.
DR EvolutionaryTrace; P06721; -.
DR PRO; PR:P06721; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:EcoCyc.
DR GO; GO:0008784; F:alanine racemase activity; IDA:EcoCyc.
DR GO; GO:0004121; F:cystathionine beta-lyase activity; IDA:EcoCyc.
DR GO; GO:0047804; F:cysteine-S-conjugate beta-lyase activity; IEA:UniProtKB-EC.
DR GO; GO:0080146; F:L-cysteine desulfhydrase activity; IDA:EcoCyc.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:EcoCyc.
DR GO; GO:0019450; P:L-cysteine catabolic process to pyruvate; IMP:EcoCyc.
DR GO; GO:0009086; P:methionine biosynthetic process; IMP:EcoCyc.
DR GO; GO:0019346; P:transsulfuration; IEA:InterPro.
DR CDD; cd00614; CGS_like; 1.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR000277; Cys/Met-Metab_PyrdxlP-dep_enz.
DR InterPro; IPR006233; Cys_b_lyase_bac.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR43500; PTHR43500; 1.
DR Pfam; PF01053; Cys_Met_Meta_PP; 1.
DR PIRSF; PIRSF001434; CGS; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR01324; cysta_beta_ly_B; 1.
DR PROSITE; PS00868; CYS_MET_METAB_PP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Cytoplasm;
KW Direct protein sequencing; Lyase; Methionine biosynthesis;
KW Pyridoxal phosphate; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..395
FT /note="Cystathionine beta-lyase MetC"
FT /id="PRO_0000114768"
FT MOD_RES 210
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:3307782,
FT ECO:0000269|PubMed:8831789"
FT HELIX 6..12
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 39..47
FT /evidence="ECO:0007829|PDB:4ITX"
FT TURN 48..52
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 57..59
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 86..97
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 112..120
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 137..143
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 148..156
FT /evidence="ECO:0007829|PDB:4ITX"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 166..176
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:4ITX"
FT TURN 187..192
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 196..199
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:4ITX"
FT TURN 208..213
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:2FQ6"
FT STRAND 221..225
FT /evidence="ECO:0007829|PDB:4ITX"
FT TURN 227..229
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 230..239
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 246..256
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 259..278
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 297..303
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 309..317
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 321..328
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 346..350
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 352..356
FT /evidence="ECO:0007829|PDB:4ITX"
FT STRAND 370..374
FT /evidence="ECO:0007829|PDB:4ITX"
FT HELIX 380..392
FT /evidence="ECO:0007829|PDB:4ITX"
SQ SEQUENCE 395 AA; 43212 MW; FD3308423D6427C6 CRC64;
MADKKLDTQL VNAGRSKKYT LGAVNSVIQR ASSLVFDSVE AKKHATRNRA NGELFYGRRG
TLTHFSLQQA MCELEGGAGC VLFPCGAAAV ANSILAFIEQ GDHVLMTNTA YEPSQDFCSK
ILSKLGVTTS WFDPLIGADI VKHLQPNTKI VFLESPGSIT MEVHDVPAIV AAVRSVVPDA
IIMIDNTWAA GVLFKALDFG IDVSIQAATK YLVGHSDAMI GTAVCNARCW EQLRENAYLM
GQMVDADTAY ITSRGLRTLG VRLRQHHESS LKVAEWLAEH PQVARVNHPA LPGSKGHEFW
KRDFTGSSGL FSFVLKKKLN NEELANYLDN FSLFSMAYSW GGYESLILAN QPEHIAAIRP
QGEIDFSGTL IRLHIGLEDV DDLIADLDAG FARIV
