ISCSL_MYCTU
ID ISCSL_MYCTU Reviewed; 393 AA.
AC P9WQ71; F2GP44; L0TE93; O53272; Q7D698;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=IscS-like cysteine desulfurase {ECO:0000303|PubMed:17609386};
DE EC=2.8.1.7 {ECO:0000269|PubMed:24548275};
GN Name=iscS; OrderedLocusNames=Rv3025c;
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 FUNCTION AS A CYSTEINE DESULFURASE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17609386; DOI=10.1073/pnas.0700490104;
RA Singh A., Guidry L., Narasimhulu K.V., Mai D., Trombley J., Redding K.E.,
RA Giles G.I., Lancaster J.R. Jr., Steyn A.J.;
RT "Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its
RT [4Fe-4S] cluster and is essential for nutrient starvation survival.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:11562-11567(2007).
RN [3]
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 [4]
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 2-393, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DISRUPTION PHENOTYPE, SUBUNIT, AND
RP SUBSTRATE SPECIFICITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=24548275; DOI=10.1042/bj20130732;
RA Rybniker J., Pojer F., Marienhagen J., Kolly G.S., Chen J.M.,
RA van Gumpel E., Hartmann P., Cole S.T.;
RT "The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in
RT iron-sulfur cluster biogenesis and oxidative stress defence.";
RL Biochem. J. 459:467-478(2014).
CC -!- FUNCTION: Catalyzes the removal of elemental sulfur from cysteine to
CC produce alanine (Probable). Participates in the biosynthesis of
CC metalloclusters by providing the inorganic sulfur required for Fe-S
CC core formation. One acceptor is Whib3, on which this enzyme assembles a
CC 4Fe-4S cluster. It can use both L-cysteine and L-selenocysteine as
CC substrates. {ECO:0000269|PubMed:17609386, ECO:0000269|PubMed:24548275}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[sulfur carrier]-H + L-cysteine = [sulfur carrier]-SH + L-
CC alanine; Xref=Rhea:RHEA:43892, Rhea:RHEA-COMP:14737, Rhea:RHEA-
CC COMP:14739, ChEBI:CHEBI:29917, ChEBI:CHEBI:35235, ChEBI:CHEBI:57972,
CC ChEBI:CHEBI:64428; EC=2.8.1.7;
CC Evidence={ECO:0000269|PubMed:24548275};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P0A6B9, ECO:0000305|PubMed:24548275};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.1 mM for L-cysteine (at pH 7.5 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:24548275};
CC -!- SUBUNIT: Homodimer. It interacts with Whib3, Acn, SdhB, FdhF and SirA,
CC other S acceptors. {ECO:0000269|PubMed:24548275}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are microaerophilic and
CC hypersensitive to oxidative stress. Moreover, they show impaired Fe-S
CC cluster-dependent enzyme activity. {ECO:0000269|PubMed:24548275}.
CC -!- MISCELLANEOUS: IscU is absent from the mycobacterial ISC operon.
CC {ECO:0000269|PubMed:24548275}.
CC -!- SIMILARITY: Belongs to the class-V pyridoxal-phosphate-dependent
CC aminotransferase family. NifS/IscS subfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP45833.1; -; Genomic_DNA.
DR PIR; D70858; D70858.
DR RefSeq; NP_217541.1; NC_000962.3.
DR RefSeq; WP_003415911.1; NZ_NVQJ01000011.1.
DR PDB; 4ISY; X-ray; 2.59 A; A/B/C/D=2-393.
DR PDBsum; 4ISY; -.
DR AlphaFoldDB; P9WQ71; -.
DR SMR; P9WQ71; -.
DR STRING; 83332.Rv3025c; -.
DR PaxDb; P9WQ71; -.
DR GeneID; 887677; -.
DR KEGG; mtu:Rv3025c; -.
DR TubercuList; Rv3025c; -.
DR eggNOG; COG1104; Bacteria.
DR OMA; KGLYWAR; -.
DR PhylomeDB; P9WQ71; -.
DR SABIO-RK; P9WQ71; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0031071; F:cysteine desulfurase activity; IDA:MTBBASE.
DR GO; GO:0051536; F:iron-sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0008483; F:transaminase activity; IEA:UniProtKB-KW.
DR GO; GO:0044571; P:[2Fe-2S] cluster assembly; IEA:InterPro.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IDA:MTBBASE.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR000192; Aminotrans_V_dom.
DR InterPro; IPR010240; Cys_deSase_IscS.
DR InterPro; IPR016454; Cysteine_dSase.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR11601:SF34; PTHR11601:SF34; 1.
DR Pfam; PF00266; Aminotran_5; 1.
DR PIRSF; PIRSF005572; NifS; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminotransferase; Iron; Iron-sulfur; Metal-binding;
KW Pyridoxal phosphate; Reference proteome; Transferase.
FT CHAIN 1..393
FT /note="IscS-like cysteine desulfurase"
FT /id="PRO_0000420404"
FT ACT_SITE 329
FT /note="Cysteine persulfide intermediate"
FT /evidence="ECO:0000250|UniProtKB:P0A6B7,
FT ECO:0000305|PubMed:24548275"
FT BINDING 68..69
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 154
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:O29689"
FT BINDING 182
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 202..204
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 240
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9"
FT BINDING 329
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /note="via persulfide group"
FT /evidence="ECO:0000250|UniProtKB:O29689"
FT MOD_RES 205
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P0A6B9,
FT ECO:0000305|PubMed:24548275"
FT TURN 6..8
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 35..54
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 62..67
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 68..86
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 101..114
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 131..139
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:4ISY"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 162..171
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:4ISY"
FT TURN 181..186
FT /evidence="ECO:0007829|PDB:4ISY"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 197..202
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 213..217
FT /evidence="ECO:0007829|PDB:4ISY"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 243..258
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 260..281
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 299..304
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 309..318
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 338..342
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:4ISY"
FT STRAND 353..357
FT /evidence="ECO:0007829|PDB:4ISY"
FT HELIX 364..385
FT /evidence="ECO:0007829|PDB:4ISY"
SQ SEQUENCE 393 AA; 40947 MW; D8CF10B6F88C85A1 CRC64;
MAYLDHAATT PMHPAAIEAM AAVQRTIGNA SSLHTSGRSA RRRIEEAREL IADKLGARPS
EVIFTAGGTE SDNLAVKGIY WARRDAEPHR RRIVTTEVEH HAVLDSVNWL VEHEGAHVTW
LPTAADGSVS ATALREALQS HDDVALVSVM WANNEVGTIL PIAEMSVVAM EFGVPMHSDA
IQAVGQLPLD FGASGLSAMS VAGHKFGGPP GVGALLLRRD VTCVPLMHGG GQERDIRSGT
PDVASAVGMA TAAQIAVDGL EENSARLRLL RDRLVEGVLA EIDDVCLNGA DDPMRLAGNA
HFTFRGCEGD ALLMLLDANG IECSTGSACT AGVAQPSHVL IAMGVDAASA RGSLRLSLGH
TSVEADVDAA LEVLPGAVAR ARRAALAAAG ASR
