SIR_MYCTU
ID SIR_MYCTU Reviewed; 555 AA.
AC P9WJ03; L0T9H3; P71753; Q7D781;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Sulfite reductase [ferredoxin];
DE EC=1.8.7.1 {ECO:0000269|PubMed:15917234};
GN Name=sir; Synonyms=nirA; OrderedLocusNames=Rv2391;
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 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 [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 (2.8 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, SUBUNIT, AND MUTAGENESIS OF TYR-69 AND CYS-161.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15917234; DOI=10.1074/jbc.m502560200;
RA Schnell R., Sandalova T., Hellman U., Lindqvist Y., Schneider G.;
RT "Siroheme- and [Fe4-S4]-dependent NirA from Mycobacterium tuberculosis is a
RT sulfite reductase with a covalent Cys-Tyr bond in the active site.";
RL J. Biol. Chem. 280:27319-27328(2005).
CC -!- FUNCTION: Catalyzes the reduction of sulfite to sulfide, a step in the
CC biosynthesis of sulfur-containing amino acids and cofactors.
CC {ECO:0000269|PubMed:15917234}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 H2O + hydrogen sulfide + 6 oxidized [2Fe-2S]-[ferredoxin] =
CC 7 H(+) + 6 reduced [2Fe-2S]-[ferredoxin] + sulfite;
CC Xref=Rhea:RHEA:23132, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17359,
CC ChEBI:CHEBI:29919, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; EC=1.8.7.1;
CC Evidence={ECO:0000269|PubMed:15917234};
CC -!- COFACTOR:
CC Name=siroheme; Xref=ChEBI:CHEBI:60052;
CC Evidence={ECO:0000269|PubMed:15917234};
CC Note=Binds 1 siroheme per subunit. {ECO:0000269|PubMed:15917234};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:15917234};
CC Note=Binds 1 [4Fe-4S] cluster per subunit.
CC {ECO:0000269|PubMed:15917234};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:15917234}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the nitrite and sulfite reductase 4Fe-4S domain
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP45179.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL123456; CCP45179.1; ALT_INIT; Genomic_DNA.
DR PIR; B70682; B70682.
DR RefSeq; NP_216907.1; NC_000962.3.
DR RefSeq; WP_003899303.1; NC_018143.2.
DR PDB; 1ZJ8; X-ray; 2.80 A; A/B=3-555.
DR PDB; 1ZJ9; X-ray; 2.90 A; A/B=3-555.
DR PDBsum; 1ZJ8; -.
DR PDBsum; 1ZJ9; -.
DR AlphaFoldDB; P9WJ03; -.
DR SMR; P9WJ03; -.
DR STRING; 83332.Rv2391; -.
DR PaxDb; P9WJ03; -.
DR DNASU; 885472; -.
DR GeneID; 45426377; -.
DR GeneID; 885472; -.
DR KEGG; mtu:Rv2391; -.
DR TubercuList; Rv2391; -.
DR eggNOG; COG0155; Bacteria.
DR OMA; MGMTHGD; -.
DR BRENDA; 1.8.7.1; 3445.
DR Reactome; R-MTU-936721; Cysteine synthesis from O-acetylserine.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:MTBBASE.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050311; F:sulfite reductase (ferredoxin) activity; IEA:UniProtKB-EC.
DR GO; GO:0016002; F:sulfite reductase activity; IDA:MTBBASE.
DR GO; GO:0000103; P:sulfate assimilation; IMP:MTBBASE.
DR Gene3D; 3.30.413.10; -; 2.
DR InterPro; IPR005117; NiRdtase/SiRdtase_haem-b_fer.
DR InterPro; IPR036136; Nit/Sulf_reduc_fer-like_dom_sf.
DR InterPro; IPR006067; NO2/SO3_Rdtase_4Fe4S_dom.
DR InterPro; IPR045854; NO2/SO3_Rdtase_4Fe4S_sf.
DR InterPro; IPR006066; NO2/SO3_Rdtase_FeS/sirohaem_BS.
DR Pfam; PF01077; NIR_SIR; 2.
DR Pfam; PF03460; NIR_SIR_ferr; 2.
DR PRINTS; PR00397; SIROHAEM.
DR SUPFAM; SSF55124; SSF55124; 2.
DR SUPFAM; SSF56014; SSF56014; 2.
DR PROSITE; PS00365; NIR_SIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Heme; Iron; Iron-sulfur; Metal-binding;
KW Oxidoreductase; Reference proteome; Thioether bond.
FT CHAIN 1..555
FT /note="Sulfite reductase [ferredoxin]"
FT /id="PRO_0000199952"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 417
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT BINDING 423
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT BINDING 463
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT BINDING 467
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT BINDING 467
FT /ligand="siroheme"
FT /ligand_id="ChEBI:CHEBI:60052"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT CROSSLNK 69..161
FT /note="3'-(S-cysteinyl)-tyrosine (Tyr-Cys)"
FT MUTAGEN 69
FT /note="Y->A,F: Strong decrease in activity."
FT /evidence="ECO:0000269|PubMed:15917234"
FT MUTAGEN 161
FT /note="C->A,S: Strong decrease in activity."
FT /evidence="ECO:0000269|PubMed:15917234"
FT HELIX 15..17
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 25..29
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 38..44
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 46..49
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 51..53
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 56..60
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 62..66
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 90..99
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 107..120
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 143..151
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 160..170
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT TURN 172..176
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 185..195
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 208..216
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 223..232
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT TURN 233..235
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 236..243
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 255..261
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 266..280
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 291..298
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 300..310
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 333..337
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 340..347
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 355..368
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 381..386
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 388..400
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 404..406
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 409..413
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 414..416
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 431..444
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 446..449
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 458..463
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 473..487
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 489..498
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT STRAND 500..502
FT /evidence="ECO:0007829|PDB:1ZJ9"
FT TURN 518..520
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 521..534
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 542..548
FT /evidence="ECO:0007829|PDB:1ZJ8"
FT HELIX 551..554
FT /evidence="ECO:0007829|PDB:1ZJ8"
SQ SEQUENCE 555 AA; 62112 MW; 68925CA37C131BC3 CRC64;
MTTARPAKAR NEGQWALGHR EPLNANEELK KAGNPLDVRE RIENIYAKQG FDSIDKTDLR
GRFRWWGLYT QREQGYDGTW TGDDNIDKLE AKYFMMRVRC DGGALSAAAL RTLGQISTEF
ARDTADISDR QNVQYHWIEV ENVPEIWRRL DDVGLQTTEA CGDCPRVVLG SPLAGESLDE
VLDPTWAIEE IVRRYIGKPD FADLPRKYKT AISGLQDVAH EINDVAFIGV NHPEHGPGLD
LWVGGGLSTN PMLAQRVGAW VPLGEVPEVW AAVTSVFRDY GYRRLRAKAR LKFLIKDWGI
AKFREVLETE YLKRPLIDGP APEPVKHPID HVGVQRLKNG LNAVGVAPIA GRVSGTILTA
VADLMARAGS DRIRFTPYQK LVILDIPDAL LDDLIAGLDA LGLQSRPSHW RRNLMACSGI
EFCKLSFAET RVRAQHLVPE LERRLEDINS QLDVPITVNI NGCPNSCARI QIADIGFKGQ
MIDDGHGGSV EGFQVHLGGH LGLDAGFGRK LRQHKVTSDE LGDYIDRVVR NFVKHRSEGE
RFAQWVIRAE EDDLR
