CYSK2_MYCTU
ID CYSK2_MYCTU Reviewed; 372 AA.
AC Q79FV4; L0T531;
DT 30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=S-sulfocysteine synthase {ECO:0000303|PubMed:25022854};
DE EC=2.8.5.1 {ECO:0000269|PubMed:25022854};
DE AltName: Full=O-phospho-L-serine-dependent S-sulfocysteine synthase {ECO:0000303|PubMed:25022854};
DE Short=OPS-dependent S-sulfocysteine synthase {ECO:0000303|PubMed:25022854};
DE AltName: Full=O-phosphoserine sulfhydrylase {ECO:0000303|PubMed:25022854};
DE EC=2.5.1.65 {ECO:0000269|PubMed:25022854};
GN Name=cysK2 {ECO:0000303|PubMed:25022854}; OrderedLocusNames=Rv0848;
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 IDENTIFICATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12368430; DOI=10.1099/00221287-148-10-2967;
RA Camus J.-C., Pryor M.J., Medigue C., Cole S.T.;
RT "Re-annotation of the genome sequence of Mycobacterium tuberculosis
RT H37Rv.";
RL Microbiology 148:2967-2973(2002).
RN [3]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, COFACTOR, PATHWAY, SUBUNIT, REACTION MECHANISM, AND MUTAGENESIS
RP OF ARG-243.
RX PubMed=25022854; DOI=10.1128/jb.01851-14;
RA Steiner E.M., Boeth D., Loessl P., Vilaplana F., Schnell R., Schneider G.;
RT "CysK2 from Mycobacterium tuberculosis is an O-phospho-L-serine-dependent
RT S-sulfocysteine synthase.";
RL J. Bacteriol. 196:3410-3420(2014).
CC -!- FUNCTION: Catalyzes the synthesis of S-sulfocysteine, utilizing O-
CC phosphoserine (OPS) and thiosulfate as substrates. To a lesser extent,
CC can also use sulfide as donor substrate, producing L-cysteine. CysK2
CC thus provides a third metabolic route to cysteine, either directly
CC using sulfide as donor or indirectly via S-sulfocysteine. S-
CC sulfocysteine might also act as a signaling molecule triggering
CC additional responses in redox defense in the pathogen upon exposure to
CC reactive oxygen species during intracellular survival or dormancy.
CC Cannot utilize thiocarboxylated CysO as a sulfur donor and O-
CC acetylserine (OAS) as acceptor substrate.
CC {ECO:0000269|PubMed:25022854}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O-phospho-L-serine + thiosulfate = phosphate + S-sulfo-L-
CC cysteine; Xref=Rhea:RHEA:52420, ChEBI:CHEBI:33542, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57524, ChEBI:CHEBI:62225; EC=2.8.5.1;
CC Evidence={ECO:0000269|PubMed:25022854};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52421;
CC Evidence={ECO:0000305|PubMed:25022854};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hydrogen sulfide + O-phospho-L-serine = L-cysteine +
CC phosphate; Xref=Rhea:RHEA:10252, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29919, ChEBI:CHEBI:35235, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57524; EC=2.5.1.65;
CC Evidence={ECO:0000269|PubMed:25022854};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10253;
CC Evidence={ECO:0000305|PubMed:25022854};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:25022854};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=135 uM for O-phospho-L-serine (in the presence of sulfide as
CC cosubstrate) {ECO:0000269|PubMed:25022854};
CC KM=374 uM for sulfide {ECO:0000269|PubMed:25022854};
CC KM=1085 uM for O-phospho-L-serine (in the presence of thiosulfate as
CC cosubstrate) {ECO:0000269|PubMed:25022854};
CC KM=43.9 uM for thiosulfate {ECO:0000269|PubMed:25022854};
CC Note=kcat is 12.1 min(-1) with O-phospho-L-serine and sulfide as
CC substrates. kcat is 54.8 min(-1) with O-phospho-L-serine and
CC thiosulfate as substrates. {ECO:0000269|PubMed:25022854};
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis.
CC {ECO:0000305|PubMed:25022854}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25022854}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- MISCELLANEOUS: The enzyme uses a mechanism via a central aminoacrylate
CC intermediate that is similar to that of other members of this pyridoxal
CC phosphate-dependent enzyme family. {ECO:0000269|PubMed:25022854}.
CC -!- SIMILARITY: Belongs to the cysteine synthase/cystathionine beta-
CC synthase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43596.1; -; Genomic_DNA.
DR PIR; H70813; H70813.
DR RefSeq; WP_009935595.1; NZ_NVQJ01000040.1.
DR RefSeq; YP_177762.1; NC_000962.3.
DR AlphaFoldDB; Q79FV4; -.
DR SMR; Q79FV4; -.
DR STRING; 83332.Rv0848; -.
DR PaxDb; Q79FV4; -.
DR DNASU; 885545; -.
DR GeneID; 885545; -.
DR KEGG; mtu:Rv0848; -.
DR PATRIC; fig|83332.111.peg.940; -.
DR TubercuList; Rv0848; -.
DR eggNOG; COG0031; Bacteria.
DR OMA; GSWCPDQ; -.
DR PhylomeDB; Q79FV4; -.
DR BioCyc; MetaCyc:G185E-5002-MON; -.
DR BRENDA; 2.5.1.47; 3445.
DR BRENDA; 2.5.1.65; 3445.
DR Reactome; R-MTU-936721; Cysteine synthesis from O-acetylserine.
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:0009274; C:peptidoglycan-based cell wall; HDA: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:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IDA:UniProtKB.
DR GO; GO:0019344; P:cysteine biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006535; P:cysteine biosynthetic process from serine; TAS:Reactome.
DR Gene3D; 3.40.50.1100; -; 2.
DR InterPro; IPR001926; PLP-dep.
DR InterPro; IPR036052; Trypto_synt_PLP_dependent.
DR Pfam; PF00291; PALP; 1.
DR SUPFAM; SSF53686; SSF53686; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Cysteine biosynthesis; Pyridoxal phosphate;
KW Reference proteome; Transferase.
FT CHAIN 1..372
FT /note="S-sulfocysteine synthase"
FT /id="PRO_0000401201"
FT BINDING 201..205
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P9WP55"
FT BINDING 288
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P9WP55"
FT MOD_RES 65
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P9WP55,
FT ECO:0000305|PubMed:25022854"
FT MUTAGEN 243
FT /note="R->A: 10-fold decrease in the specificity constant
FT for thiosulfate compared to wild-type enzyme but little
FT change in the specificity constant for the substrate OPS."
FT /evidence="ECO:0000269|PubMed:25022854"
SQ SEQUENCE 372 AA; 40118 MW; 927386BE1DF5FB6C CRC64;
MRSRQTRDRY RLLPEGYQVT PGRNRHPGTM VGNTPVLWIP ELSGTSDPDR GFWAKLEGFN
PGGMKDRPAL YMVECARARG DIAPGAAIVE STGGTLGLGL ALAGKVYRHP VTLVTDPGLE
PIIARMLTAY GAGVDMVTQP HPVGGWQQAR KDRVAQLMAE YPGAWNPNQY GNPDNVGAYR
SLALELVAQL GRIDVLVCSV GTGGHSAGVA RVLREFNPDM RLIGVDTIGS TIFGQPASNR
LMRGLGSSIY PRNVDYRAFD EVHWVAPPEA VWACRSLAAT HYASGGWSVG AVALVAGWAA
RNLPADTTIA AVFPDGPQRY FDTIYNDAYC NEHELLGGQP PTEPDEIASP LDAVVTRWTR
STTVIDPTQV VS
