O-phosphoserine sulfhydrylase - Mycobacterium tuberculosis

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P63873 (CYSM_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 52. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
O-phosphoserine sulfhydrylase
Short name=OPS sulfhydrylase
EC=2.5.1.65
EC=2.5.1.n5

Alternative name(s):
CysO-thiocarboxylate-dependent cysteine synthase
Cysteine synthase B
Short name=CSase B
O-phosphoserine-specific cysteine synthase

Gene names

Name:	cysM
Ordered Locus Names:	Rv1336, MT1377
ORF Names:	MTCY130.21

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the formation of a covalent CysO-cysteine adduct via a sulfur transfer, using the thiocarboxylated sulfur carrier protein CysO-COSH as sulfur donor and O-phospho-L-serine (OPS) as sulfur acceptor. Can also use sodium sulfide as sulfur donor in vitro, albeit with less efficiency, but not thiosulfate or thio-nitro-benzoate. O-acetylserine (OAS) is a very poor substrate in comparison with OPS. May be of particular importance for cysteine biosynthesis in the persistent phase of M.tuberculosis. Ref.5 Ref.7
Catalytic activity	O-phospho-L-serine + H₂S = L-cysteine + phosphate. Ref.5 Ref.7 Ref.8 O-phospho-L-serine + [CysO]-SH = [CysO]-L-cysteine + phosphate. Ref.5 Ref.7 Ref.8
Cofactor	Pyridoxal phosphate. Ref.7
Pathway	Amino-acid biosynthesis; L-cysteine biosynthesis.
Subunit structure	Homodimer. Ref.7
Induction	Up-regulated under oxidative stress conditions. Ref.3
Domain	The five C-terminal amino acid residues are inserted into the active site cleft in the closed conformation, protect the aminoacrylate intermediate and are involved in sulfur donor selectivity. Ref.8
Disruption phenotype	Strains lacking this gene are shown to be attenuated in macrophages. Ref.4
Sequence similarities	Belongs to the cysteine synthase/cystathionine beta-synthase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Cysteine biosynthesis
Ligand	Pyridoxal phosphate
Molecular function	Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cysteine biosynthetic process from serine Inferred from direct assay Ref.7. Source: MTBBASE
Cellular component	cytosol Traceable author statement. Source: Reactome protein complex Inferred from direct assay Ref.6. Source: MTBBASE
Molecular function	O-phosphoserine sulfhydrylase activity Inferred from direct assay Ref.7. Source: MTBBASE cysteine synthase activity Inferred from electronic annotation. Source: InterPro protein homodimerization activity Inferred from physical interaction Ref.7. Source: MTBBASE pyridoxal phosphate binding Inferred from direct assay Ref.7. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 323

323

O-phosphoserine sulfhydrylase

PRO_0000167112

Regions

Region

184 – 188

Pyridoxal phosphate binding

Sites

Binding site

Pyridoxal phosphate

Binding site

220

Substrate Probable

Binding site

265

Pyridoxal phosphate

Amino acid modifications

Modified residue

N6-(pyridoxal phosphate)lysine

Experimental info

Mutagenesis

220

R → A: 700-fold decrease in the rate of the first half-reaction using OPS. Affects neither the rate of the first half-reaction using OAS nor the rate of the second half-reaction using sulfide or CysO-COSH. Ref.7

Mutagenesis

319 – 323

Missing: Decreased lifetime of the alpha-aminoacrylate reaction intermediate, increased susceptibility to oxidation by oxidative agents such as hydrogen peroxide, and partial loss of selectivity towards CysO-COSH as sulfur donor. Ref.8

Secondary structure

323

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P63873 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: B743231FEFA87573
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FASTA

323

34,438

        10         20         30         40         50         60 
MTRYDSLLQA LGNTPLVGLQ RLSPRWDDGR DGPHVRLWAK LEDRNPTGSI KDRPAVRMIE 

        70         80         90        100        110        120 
QAEADGLLRP GATILEPTSG NTGISLAMAA RLKGYRLICV MPENTSVERR QLLELYGAQI 

       130        140        150        160        170        180 
IFSAAEGGSN TAVATAKELA ATNPSWVMLY QYGNPANTDS HYCGTGPELL ADLPEITHFV 

       190        200        210        220        230        240 
AGLGTTGTLM GTGRFLREHV ANVKIVAAEP RYGEGVYALR NMDEGFVPEL YDPEILTARY 

       250        260        270        280        290        300 
SVGAVDAVRR TRELVHTEGI FAGISTGAVL HAALGVGAGA LAAGERADIA LVVADAGWKY 

       310        320 
LSTGAYAGSL DDAETALEGQ LWA

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. Barrell B.G. Nature 393:537-544(1998) [PubMed: 9634230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Role of the extracytoplasmic-function sigma factor sigma(H) in Mycobacterium tuberculosis global gene expression." Manganelli R., Voskuil M.I., Schoolnik G.K., Dubnau E., Gomez M., Smith I. Mol. Microbiol. 45:365-374(2002) [PubMed: 12123450] [Abstract] Cited for: INDUCTION. Strain: ATCC 25618 / H37Rv.
[4]	"Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages." Rengarajan J., Bloom B.R., Rubin E.J. Proc. Natl. Acad. Sci. U.S.A. 102:8327-8332(2005) [PubMed: 15928073] [Abstract] Cited for: DISRUPTION PHENOTYPE. Strain: ATCC 25618 / H37Rv.
[5]	"O-phospho-L-serine and the thiocarboxylated sulfur carrier protein CysO-COSH are substrates for CysM, a cysteine synthase from Mycobacterium tuberculosis." O'Leary S.E., Jurgenson C.T., Ealick S.E., Begley T.P. Biochemistry 47:11606-11615(2008) [PubMed: 18842002] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, KINETIC STUDIES, REACTION MECHANISM.
[6]	"Crystal structure of a sulfur carrier protein complex found in the cysteine biosynthetic pathway of Mycobacterium tuberculosis." Jurgenson C.T., Burns K.E., Begley T.P., Ealick S.E. Biochemistry 47:10354-10364(2008) [PubMed: 18771296] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF WILD-TYPE AND MUTANT ALA-204 IN COMPLEX WITH PYRIDOXAL PHOSPHATE AND PROTEIN CYSO, REACTION MECHANISM.
[7]	"Cysteine synthase (CysM) of Mycobacterium tuberculosis is an O-phosphoserine sulfhydrylase: evidence for an alternative cysteine biosynthesis pathway in mycobacteria." Agren D., Schnell R., Oehlmann W., Singh M., Schneider G. J. Biol. Chem. 283:31567-31574(2008) [PubMed: 18799456] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 3-323 IN COMPLEX WITH PYRIDOXAL PHOSPHATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY, SUBUNIT, MUTAGENESIS OF ARG-220. Strain: ATCC 25618 / H37Rv.
[8]	"The C-terminal of CysM from Mycobacterium tuberculosis protects the aminoacrylate intermediate and is involved in sulfur donor selectivity." Agren D., Schnell R., Schneider G. FEBS Lett. 583:330-336(2009) [PubMed: 19101553] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 3-323 IN COMPLEX WITH PYRIDOXAL PHOSPHATE, CATALYTIC ACTIVITY, DOMAIN, MUTAGENESIS OF 319-GLY--ALA-323. Strain: ATCC 25618 / H37Rv.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842576 Genomic DNA. Translation: CAA98100.1.
AE000516 Genomic DNA. Translation: AAK45642.1.

PIR

D70771.

RefSeq

NP_215852.1. NC_000962.2.
NP_335828.1. NC_002755.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DKI	X-ray	2.10	A/B	3-323	[»]
3DWG	X-ray	1.53	A/B	1-323	[»]
3DWI	X-ray	2.81	A/B	1-323	[»]
3FGP	X-ray	2.05	A/B	3-323	[»]

ProteinModelPortal

P63873.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBMYCT00000001280; EBMYCP00000001280; EBMYCG00000001280.
EBMYCT00000069828; EBMYCP00000067887; EBMYCG00000069823.

GeneID

886867.
924673.

GenomeReviews

Gene locus MT1377 in contig AE000516_GR.
Gene locus Rv1336 in contig AL123456_GR.

KEGG

mtc:MT1377.
mtu:Rv1336.

PATRIC

18124802. VBIMycTub22151_1516.

TIGR

MT1377.

Organism-specific databases

TubercuList

Rv1336.

Phylogenomic databases

GeneTree

EBGT00050000015764.

HOGENOM

HBG748215.

OMA

YSVGPRE.

PhylomeDB

P63873.

ProtClustDB

CLSK871928.

Enzyme and pathway databases

Reactome

REACT_27295. Mycobacterium tuberculosis biological processes.

Family and domain databases

InterPro

IPR001216. Cys_synth_BS.
IPR005856. Cys_synthKM.
IPR001926. PyrdxlP-dep_enz_bsu.
[Graphical view]

K12339.

Pfam

PF00291. PALP. 1 hit.
[Graphical view]

SUPFAM

SSF53686. PyrdxlP-dep_enz_bsu. 1 hit.

TIGRFAMs

TIGR01136. CysKM. 1 hit.

PROSITE

PS00901. CYS_SYNTHASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

CYSM_MYCTU

Accession

Primary (citable) accession number: P63873
Secondary accession number(s): Q10624

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	January 25, 2012
This is version 52 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents