CYSM_MYCTU
ID CYSM_MYCTU Reviewed; 323 AA.
AC P9WP53; L0T934; P63873; Q10624;
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=O-phosphoserine sulfhydrylase {ECO:0000303|PubMed:18799456};
DE Short=OPS sulfhydrylase;
DE EC=2.5.1.113 {ECO:0000269|PubMed:18799456, ECO:0000269|PubMed:18842002, ECO:0000269|PubMed:19101553};
DE AltName: Full=CysO-thiocarboxylate-dependent cysteine synthase;
DE AltName: Full=Cysteine synthase B;
DE Short=CSase B;
DE AltName: Full=O-phosphoserine-specific cysteine synthase;
DE AltName: Full=[CysO sulfur-carrier protein]-thiocarboxylate-dependent cysteine synthase;
GN Name=cysM; OrderedLocusNames=Rv1336; ORFNames=MTCY130.21;
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 [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 [2]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12123450; DOI=10.1046/j.1365-2958.2002.03005.x;
RA Manganelli R., Voskuil M.I., Schoolnik G.K., Dubnau E., Gomez M., Smith I.;
RT "Role of the extracytoplasmic-function sigma factor sigma(H) in
RT Mycobacterium tuberculosis global gene expression.";
RL Mol. Microbiol. 45:365-374(2002).
RN [3]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15928073; DOI=10.1073/pnas.0503272102;
RA Rengarajan J., Bloom B.R., Rubin E.J.;
RT "Genome-wide requirements for Mycobacterium tuberculosis adaptation and
RT survival in macrophages.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8327-8332(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, KINETIC STUDIES, AND
RP REACTION MECHANISM.
RX PubMed=18842002; DOI=10.1021/bi8013664;
RA O'Leary S.E., Jurgenson C.T., Ealick S.E., Begley T.P.;
RT "O-phospho-L-serine and the thiocarboxylated sulfur carrier protein CysO-
RT COSH are substrates for CysM, a cysteine synthase from Mycobacterium
RT tuberculosis.";
RL Biochemistry 47:11606-11615(2008).
RN [5]
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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF WILD-TYPE AND MUTANT ALA-204 IN
RP COMPLEX WITH PYRIDOXAL PHOSPHATE AND PROTEIN CYSO, AND REACTION MECHANISM.
RX PubMed=18771296; DOI=10.1021/bi800915j;
RA Jurgenson C.T., Burns K.E., Begley T.P., Ealick S.E.;
RT "Crystal structure of a sulfur carrier protein complex found in the
RT cysteine biosynthetic pathway of Mycobacterium tuberculosis.";
RL Biochemistry 47:10354-10364(2008).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 3-323 IN COMPLEX WITH PYRIDOXAL
RP PHOSPHATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY,
RP SUBUNIT, AND MUTAGENESIS OF ARG-220.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18799456; DOI=10.1074/jbc.m804877200;
RA Agren D., Schnell R., Oehlmann W., Singh M., Schneider G.;
RT "Cysteine synthase (CysM) of Mycobacterium tuberculosis is an O-
RT phosphoserine sulfhydrylase: evidence for an alternative cysteine
RT biosynthesis pathway in mycobacteria.";
RL J. Biol. Chem. 283:31567-31574(2008).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 3-323 IN COMPLEX WITH PYRIDOXAL
RP PHOSPHATE, CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS OF 319-GLY--ALA-323.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19101553; DOI=10.1016/j.febslet.2008.12.019;
RA Agren D., Schnell R., Schneider G.;
RT "The C-terminal of CysM from Mycobacterium tuberculosis protects the
RT aminoacrylate intermediate and is involved in sulfur donor selectivity.";
RL FEBS Lett. 583:330-336(2009).
CC -!- FUNCTION: Catalyzes the formation of a covalent CysO-cysteine adduct
CC via a sulfur transfer, using the thiocarboxylated sulfur carrier
CC protein CysO-COSH as sulfur donor and O-phospho-L-serine (OPS) as
CC sulfur acceptor. Can also use sodium sulfide as sulfur donor in vitro,
CC albeit with less efficiency, but not thiosulfate or thio-nitro-
CC benzoate. O-acetylserine (OAS) is a very poor substrate in comparison
CC with OPS. May be of particular importance for cysteine biosynthesis in
CC the persistent phase of M.tuberculosis. {ECO:0000269|PubMed:18799456,
CC ECO:0000269|PubMed:18842002}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[CysO sulfur-carrier protein]-Gly-NH-CH2-C(O)SH + O-phospho-L-
CC serine = [CysO sulfur-carrier protein]-Gly-NH-CH2-C(O)-S-L-Cys +
CC phosphate; Xref=Rhea:RHEA:48740, Rhea:RHEA-COMP:12207, Rhea:RHEA-
CC COMP:12213, ChEBI:CHEBI:43474, ChEBI:CHEBI:57524, ChEBI:CHEBI:90619,
CC ChEBI:CHEBI:90783; EC=2.5.1.113;
CC Evidence={ECO:0000269|PubMed:18799456, ECO:0000269|PubMed:18842002,
CC ECO:0000269|PubMed:19101553};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:18799456};
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18771296,
CC ECO:0000269|PubMed:18799456, ECO:0000269|PubMed:19101553}.
CC -!- INDUCTION: Up-regulated under oxidative stress conditions.
CC {ECO:0000269|PubMed:12123450}.
CC -!- DOMAIN: The five C-terminal amino acid residues are inserted into the
CC active site cleft in the closed conformation, protect the aminoacrylate
CC intermediate and are involved in sulfur donor selectivity.
CC {ECO:0000269|PubMed:19101553}.
CC -!- DISRUPTION PHENOTYPE: Strains lacking this gene are shown to be
CC attenuated in macrophages. {ECO:0000269|PubMed:15928073}.
CC -!- SIMILARITY: Belongs to the cysteine synthase/cystathionine beta-
CC synthase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP44094.1; -; Genomic_DNA.
DR PIR; D70771; D70771.
DR RefSeq; NP_215852.1; NC_000962.3.
DR RefSeq; WP_003406912.1; NZ_NVQJ01000031.1.
DR PDB; 3DKI; X-ray; 2.10 A; A/B=3-323.
DR PDB; 3DWG; X-ray; 1.53 A; A/B=1-323.
DR PDB; 3DWI; X-ray; 2.81 A; A/B=1-323.
DR PDB; 3FGP; X-ray; 2.05 A; A/B=3-323.
DR PDB; 5I6D; X-ray; 1.64 A; A/B/C/D=1-323.
DR PDB; 5I7A; X-ray; 2.08 A; A/B/C/D=3-323.
DR PDB; 5I7H; X-ray; 2.57 A; A/B/C/D=1-323.
DR PDB; 5I7O; X-ray; 2.49 A; A/B/C/D=1-323.
DR PDB; 5I7R; X-ray; 1.73 A; A/B=1-323.
DR PDB; 5IW8; X-ray; 2.04 A; A/B=1-323.
DR PDB; 5IWC; X-ray; 2.70 A; A/B=1-323.
DR PDBsum; 3DKI; -.
DR PDBsum; 3DWG; -.
DR PDBsum; 3DWI; -.
DR PDBsum; 3FGP; -.
DR PDBsum; 5I6D; -.
DR PDBsum; 5I7A; -.
DR PDBsum; 5I7H; -.
DR PDBsum; 5I7O; -.
DR PDBsum; 5I7R; -.
DR PDBsum; 5IW8; -.
DR PDBsum; 5IWC; -.
DR AlphaFoldDB; P9WP53; -.
DR SMR; P9WP53; -.
DR STRING; 83332.Rv1336; -.
DR PaxDb; P9WP53; -.
DR DNASU; 886867; -.
DR GeneID; 45425314; -.
DR GeneID; 886867; -.
DR KEGG; mtu:Rv1336; -.
DR TubercuList; Rv1336; -.
DR eggNOG; COG0031; Bacteria.
DR OMA; GIRRWPE; -.
DR PhylomeDB; P9WP53; -.
DR BioCyc; MetaCyc:G185E-5515-MON; -.
DR BRENDA; 2.5.1.113; 3445.
DR BRENDA; 2.5.1.65; 3445.
DR Reactome; R-MTU-936654; Cysteine synthesis from O-phosphoserine.
DR UniPathway; UPA00136; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IDA:MTBBASE.
DR GO; GO:0004124; F:cysteine synthase activity; IBA:GO_Central.
DR GO; GO:0080146; F:L-cysteine desulfhydrase activity; IBA:GO_Central.
DR GO; GO:0033847; F:O-phosphoserine sulfhydrylase activity; IDA:MTBBASE.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:MTBBASE.
DR GO; GO:0019344; P:cysteine biosynthetic process; IBA:GO_Central.
DR GO; GO:0006535; P:cysteine biosynthetic process from serine; IDA:MTBBASE.
DR Gene3D; 3.40.50.1100; -; 2.
DR InterPro; IPR005856; Cys_synth.
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; TIGR01136; cysKM; 1.
DR PROSITE; PS00901; CYS_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Cysteine biosynthesis;
KW Pyridoxal phosphate; Reference proteome; Transferase.
FT CHAIN 1..323
FT /note="O-phosphoserine sulfhydrylase"
FT /id="PRO_0000167112"
FT BINDING 81
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:18771296,
FT ECO:0000269|PubMed:18799456, ECO:0000269|PubMed:19101553"
FT BINDING 184..188
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT BINDING 220
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 265
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:18771296,
FT ECO:0000269|PubMed:18799456, ECO:0000269|PubMed:19101553"
FT MOD_RES 51
FT /note="N6-(pyridoxal phosphate)lysine"
FT MUTAGEN 220
FT /note="R->A: 700-fold decrease in the rate of the first
FT half-reaction using OPS. Affects neither the rate of the
FT first half-reaction using OAS nor the rate of the second
FT half-reaction using sulfide or CysO-COSH."
FT /evidence="ECO:0000269|PubMed:18799456"
FT MUTAGEN 319..323
FT /note="Missing: Decreased lifetime of the alpha-
FT aminoacrylate reaction intermediate, increased
FT susceptibility to oxidation by oxidative agents such as
FT hydrogen peroxide, and partial loss of selectivity towards
FT CysO-COSH as sulfur donor."
FT /evidence="ECO:0000269|PubMed:19101553"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:3DWG"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 23..27
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 35..41
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:5IW8"
FT HELIX 52..64
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 81..93
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 96..105
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 107..116
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:3DWG"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 129..142
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:5I7R"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 155..163
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 165..172
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 178..182
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 187..199
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 204..211
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 237..243
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 244..258
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 264..283
FT /evidence="ECO:0007829|PDB:3DWG"
FT STRAND 287..293
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 297..303
FT /evidence="ECO:0007829|PDB:3DWG"
FT TURN 304..306
FT /evidence="ECO:0007829|PDB:3DWG"
FT HELIX 310..317
FT /evidence="ECO:0007829|PDB:3DWG"
SQ SEQUENCE 323 AA; 34438 MW; B743231FEFA87573 CRC64;
MTRYDSLLQA LGNTPLVGLQ RLSPRWDDGR DGPHVRLWAK LEDRNPTGSI KDRPAVRMIE
QAEADGLLRP GATILEPTSG NTGISLAMAA RLKGYRLICV MPENTSVERR QLLELYGAQI
IFSAAEGGSN TAVATAKELA ATNPSWVMLY QYGNPANTDS HYCGTGPELL ADLPEITHFV
AGLGTTGTLM GTGRFLREHV ANVKIVAAEP RYGEGVYALR NMDEGFVPEL YDPEILTARY
SVGAVDAVRR TRELVHTEGI FAGISTGAVL HAALGVGAGA LAAGERADIA LVVADAGWKY
LSTGAYAGSL DDAETALEGQ LWA
