ID CYSM_MYCTU Reviewed; 323 AA.
AC P63873; L0T934; Q10624;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 01-MAY-2013, entry version 62.
DE RecName: Full=O-phosphoserine sulfhydrylase;
DE Short=OPS sulfhydrylase;
DE EC=2.5.1.65;
DE EC=2.5.1.n5;
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;
GN Name=cysM; OrderedLocusNames=Rv1336, MT1377; ORFNames=MTCY130.21;
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 [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 [2]
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 [3]
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.,
RA 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 [4]
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
RT and survival in macrophages.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8327-8332(2005).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, KINETIC STUDIES,
RP AND 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
RT CysO-COSH are substrates for CysM, a cysteine synthase from
RT Mycobacterium tuberculosis.";
RL Biochemistry 47:11606-11615(2008).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF WILD-TYPE AND MUTANT ALA-204
RP IN COMPLEX WITH PYRIDOXAL PHOSPHATE AND PROTEIN CYSO, AND REACTION
RP 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
RP PYRIDOXAL PHOSPHATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE
RP SPECIFICITY, 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
RP PYRIDOXAL PHOSPHATE, CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS OF
RP 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
RT selectivity.";
RL FEBS Lett. 583:330-336(2009).
CC -!- FUNCTION: Catalyzes the formation of a covalent CysO-cysteine
CC adduct via a sulfur transfer, using the thiocarboxylated sulfur
CC carrier protein CysO-COSH as sulfur donor and O-phospho-L-serine
CC (OPS) as sulfur acceptor. Can also use sodium sulfide as sulfur
CC donor in vitro, albeit with less efficiency, but not thiosulfate
CC or thio-nitro-benzoate. O-acetylserine (OAS) is a very poor
CC substrate in comparison with OPS. May be of particular importance
CC for cysteine biosynthesis in the persistent phase of
CC M.tuberculosis.
CC -!- CATALYTIC ACTIVITY: O-phospho-L-serine + H(2)S = L-cysteine +
CC phosphate.
CC -!- CATALYTIC ACTIVITY: O-phospho-L-serine + [CysO]-SH = [CysO]-L-
CC cysteine + phosphate.
CC -!- COFACTOR: Pyridoxal phosphate.
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis.
CC -!- SUBUNIT: Homodimer.
CC -!- INDUCTION: Up-regulated under oxidative stress conditions.
CC -!- DOMAIN: The five C-terminal amino acid residues are inserted into
CC the active site cleft in the closed conformation, protect the
CC aminoacrylate intermediate and are involved in sulfur donor
CC selectivity.
CC -!- DISRUPTION PHENOTYPE: Strains lacking this gene are shown to be
CC attenuated in macrophages.
CC -!- SIMILARITY: Belongs to the cysteine synthase/cystathionine beta-
CC synthase family.
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DR EMBL; BX842576; CAA98100.1; -; Genomic_DNA.
DR EMBL; AE000516; AAK45642.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44094.1; -; Genomic_DNA.
DR PIR; D70771; D70771.
DR RefSeq; NP_215852.1; NC_000962.3.
DR RefSeq; NP_335828.1; NC_002755.2.
DR RefSeq; YP_006514714.1; NC_018143.1.
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 PDBsum; 3DKI; -.
DR PDBsum; 3DWG; -.
DR PDBsum; 3DWI; -.
DR PDBsum; 3FGP; -.
DR ProteinModelPortal; P63873; -.
DR SMR; P63873; 1-323.
DR STRING; 83332.Rv1336; -.
DR PRIDE; P63873; -.
DR EnsemblBacteria; AAK45642; AAK45642; MT1377.
DR GeneID; 13319922; -.
DR GeneID; 886867; -.
DR GeneID; 924673; -.
DR KEGG; mtc:MT1377; -.
DR KEGG; mtu:Rv1336; -.
DR KEGG; mtv:RVBD_1336; -.
DR PATRIC; 18124802; VBIMycTub22151_1516.
DR TubercuList; Rv1336; -.
DR eggNOG; COG0031; -.
DR HOGENOM; HOG000217394; -.
DR KO; K12339; -.
DR OMA; YSVGPRE; -.
DR ProtClustDB; CLSK871928; -.
DR Reactome; REACT_27295; Mycobacterium tuberculosis biological processes.
DR UniPathway; UPA00136; -.
DR EvolutionaryTrace; P63873; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043234; C:protein complex; IDA:MTBBASE.
DR GO; GO:0004124; F:cysteine synthase activity; IEA:InterPro.
DR GO; GO:0033847; F:O-phosphoserine sulfhydrylase activity; IDA:MTBBASE.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:MTBBASE.
DR GO; GO:0006535; P:cysteine biosynthetic process from serine; IDA:MTBBASE.
DR InterPro; IPR001216; Cys_synth_BS.
DR InterPro; IPR005856; Cys_synthKM.
DR InterPro; IPR001926; Trp_syn_b_sub_like_PLP_eny_SF.
DR Pfam; PF00291; PALP; 1.
DR SUPFAM; SSF53686; PyrdxlP-dep_enz_bsu; 1.
DR TIGRFAMs; TIGR01136; cysKM; 1.
DR PROSITE; PS00901; CYS_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Complete proteome;
KW Cysteine biosynthesis; Pyridoxal phosphate; Reference proteome;
KW Transferase.
FT CHAIN 1 323 O-phosphoserine sulfhydrylase.
FT /FTId=PRO_0000167112.
FT REGION 184 188 Pyridoxal phosphate binding.
FT BINDING 81 81 Pyridoxal phosphate.
FT BINDING 220 220 Substrate (Probable).
FT BINDING 265 265 Pyridoxal phosphate.
FT MOD_RES 51 51 N6-(pyridoxal phosphate)lysine.
FT MUTAGEN 220 220 R->A: 700-fold decrease in the rate of
FT the first half-reaction using OPS.
FT Affects neither the rate of the first
FT half-reaction using OAS nor the rate of
FT the second half-reaction using sulfide or
FT CysO-COSH.
FT MUTAGEN 319 323 Missing: Decreased lifetime of the alpha-
FT aminoacrylate reaction intermediate,
FT increased susceptibility to oxidation by
FT oxidative agents such as hydrogen
FT peroxide, and partial loss of selectivity
FT towards CysO-COSH as sulfur donor.
FT STRAND 3 6
FT HELIX 8 10
FT STRAND 16 18
FT TURN 20 22
FT STRAND 23 27
FT STRAND 35 41
FT HELIX 42 44
FT HELIX 52 64
FT STRAND 73 77
FT HELIX 81 93
FT STRAND 96 105
FT HELIX 107 116
FT STRAND 119 123
FT TURN 126 128
FT HELIX 129 142
FT STRAND 146 148
FT TURN 151 153
FT HELIX 155 163
FT HELIX 165 172
FT STRAND 178 182
FT STRAND 184 186
FT HELIX 187 199
FT STRAND 204 211
FT HELIX 214 217
FT HELIX 222 224
FT HELIX 233 235
FT STRAND 237 243
FT HELIX 244 258
FT HELIX 264 283
FT STRAND 287 293
FT HELIX 297 303
FT TURN 304 306
FT HELIX 310 317
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
//
