STXA_SHIDY
ID STXA_SHIDY Reviewed; 315 AA.
AC Q9FBI2;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Shiga toxin subunit A;
DE EC=3.2.2.22;
DE Flags: Precursor;
GN Name=stxA;
OS Shigella dysenteriae.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Shigella.
OX NCBI_TaxID=622;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Kozlov Y.V., Kabishev A.A., Fedchenko V.I., Bayev A.A.;
RT "Cloning and primary structure of Shigella toxin genes.";
RL Dokl. Biochem. 295:744-749(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2830229; DOI=10.1128/jb.170.3.1116-1122.1988;
RA Strockbine N.A., Jackson M.P., Sung L.M., Holmes R.K., O'Brien A.D.;
RT "Cloning and sequencing of the genes for Shiga toxin from Shigella
RT dysenteriae type 1.";
RL J. Bacteriol. 170:1116-1122(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3049254; DOI=10.1016/0378-1119(88)90398-8;
RA Kozlov Y.V., Kabishev A.A., Lukyanov E.V., Bayev A.A.;
RT "The primary structure of the operons coding for Shigella dysenteriae toxin
RT and temperature phage H30 shiga-like toxin.";
RL Gene 67:213-221(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=H2765-39/81 / Type 1;
RX PubMed=10948097; DOI=10.1128/iai.68.9.4856-4864.2000;
RA Unkmeir A., Schmidt H.;
RT "Structural analysis of phage-borne stx genes and their flanking sequences
RT in shiga toxin-producing Escherichia coli and Shigella dysenteriae type 1
RT strains.";
RL Infect. Immun. 68:4856-4864(2000).
RN [5]
RP EFFECT ON EUKARYOTIC RIBOSOME.
RX PubMed=3276522; DOI=10.1111/j.1432-1033.1988.tb13756.x;
RA Endo Y., Tsurugi K., Yutsudo T., Takeda Y., Ogasawara T., Igarashi K.;
RT "Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of
RT Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the
RT toxins.";
RL Eur. J. Biochem. 171:45-50(1988).
RN [6]
RP CLEAVAGE BY FURIN.
RX PubMed=7738018; DOI=10.1074/jbc.270.18.10817;
RA Garred O., van Deurs B., Sandvig K.;
RT "Furin-induced cleavage and activation of Shiga toxin.";
RL J. Biol. Chem. 270:10817-10821(1995).
RN [7]
RP MUTAGENESIS OF TRP-299; ASP-300; ARG-310 AND ARG-311.
RX PubMed=7768810; DOI=10.1128/jb.177.11.3128-3132.1995;
RA Jemal C., Haddad J.E., Begum D., Jackson M.P.;
RT "Analysis of Shiga toxin subunit association by using hybrid A polypeptides
RT and site-specific mutagenesis.";
RL J. Bacteriol. 177:3128-3132(1995).
RN [8]
RP MUTAGENESIS OF PHE-248; ALA-253; ILE-254; LEU-255 AND GLY-256.
RX PubMed=9784530; DOI=10.1128/iai.66.11.5252-5259.1998;
RA Suhan M.L., Hovde C.J.;
RT "Disruption of an internal membrane-spanning region in Shiga toxin 1
RT reduces cytotoxicity.";
RL Infect. Immun. 66:5252-5259(1998).
RN [9]
RP CRYSTALLIZATION.
RX PubMed=8345529; DOI=10.1006/jmbi.1993.1421;
RA Kozlov Y.V., Chernaia M.M., Fraser M.E., James M.N.G.;
RT "Purification and crystallization of Shiga toxin from Shigella
RT dysenteriae.";
RL J. Mol. Biol. 232:704-706(1993).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-315.
RX PubMed=7656009; DOI=10.1038/nsb0194-59;
RA Fraser M.E., Chernaia M.M., Kozlov Y.V., James M.N.G.;
RT "Crystal structure of the holotoxin from Shigella dysenteriae at 2.5 A
RT resolution.";
RL Nat. Struct. Biol. 1:59-64(1994).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-315.
RX PubMed=15075327; DOI=10.1074/jbc.m401939200;
RA Fraser M.E., Fujinaga M., Cherney M.M., Melton-Celsa A.R., Twiddy E.M.,
RA O'Brien A.D., James M.N.G.;
RT "Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7.";
RL J. Biol. Chem. 279:27511-27517(2004).
CC -!- FUNCTION: The A subunit is responsible for inhibiting protein synthesis
CC through the catalytic inactivation of 60S ribosomal subunits. After
CC endocytosis, the A subunit is cleaved by furin in two fragments, A1 and
CC A2: A1 is the catalytically active fragment, and A2 is essential for
CC holotoxin assembly with the B subunits.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endohydrolysis of the N-glycosidic bond at one specific
CC adenosine on the 28S rRNA.; EC=3.2.2.22;
CC -!- SUBUNIT: Shiga toxin contains a single subunit A and five copies of
CC subunit B.
CC -!- SIMILARITY: Belongs to the ribosome-inactivating protein family.
CC {ECO:0000305}.
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DR EMBL; X07903; CAA30741.1; -; Genomic_DNA.
DR EMBL; M19437; AAA98347.1; -; Genomic_DNA.
DR EMBL; M24352; AAA26538.1; -; Genomic_DNA.
DR EMBL; AJ271153; CAC05622.1; -; Genomic_DNA.
DR RefSeq; WP_000691354.1; NZ_UAUQ01000013.1.
DR PDB; 1DM0; X-ray; 2.50 A; A/L=23-309.
DR PDB; 1R4Q; X-ray; 2.50 A; A/L=23-315.
DR PDBsum; 1DM0; -.
DR PDBsum; 1R4Q; -.
DR AlphaFoldDB; Q9FBI2; -.
DR SMR; Q9FBI2; -.
DR BindingDB; Q9FBI2; -.
DR ChEMBL; CHEMBL3879822; -.
DR UniLectin; Q9FBI2; -.
DR BioCyc; MetaCyc:MON-18743; -.
DR EvolutionaryTrace; Q9FBI2; -.
DR GO; GO:0030598; F:rRNA N-glycosylase activity; IEA:UniProtKB-EC.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0017148; P:negative regulation of translation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.420.10; -; 1.
DR Gene3D; 4.10.470.10; -; 1.
DR InterPro; IPR036041; Ribosome-inact_prot_sf.
DR InterPro; IPR001574; Ribosome_inactivat_prot.
DR InterPro; IPR017988; Ribosome_inactivat_prot_CS.
DR InterPro; IPR016138; Ribosome_inactivat_prot_sub1.
DR InterPro; IPR016139; Ribosome_inactivat_prot_sub2.
DR InterPro; IPR016331; Shiga-like_toxin_subunit_A.
DR Pfam; PF00161; RIP; 1.
DR PIRSF; PIRSF001924; Shigella_toxin_subunit_A; 1.
DR SUPFAM; SSF56371; SSF56371; 1.
DR PROSITE; PS00275; SHIGA_RICIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Hydrolase; Protein synthesis inhibitor;
KW Signal; Toxin; Virulence.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..315
FT /note="Shiga toxin subunit A"
FT /id="PRO_0000312302"
FT REGION 23..273
FT /note="A1"
FT REGION 274..315
FT /note="A2"
FT ACT_SITE 189
FT SITE 273..274
FT /note="Cleavage; by furin"
FT DISULFID 264..283
FT /evidence="ECO:0000250"
FT MUTAGEN 248
FT /note="F->Y: No effect on enzymatic activity; 10-fold
FT decrease in cytotoxicity."
FT /evidence="ECO:0000269|PubMed:9784530"
FT MUTAGEN 253
FT /note="A->D: 225-fold decrease in cytotoxicity, probably
FT due to reduced translocation across the ER membrane; when
FT associated with E-256."
FT /evidence="ECO:0000269|PubMed:9784530"
FT MUTAGEN 253
FT /note="A->D: No effect on enzymatic activity; slight
FT decrease in cytotoxicity."
FT /evidence="ECO:0000269|PubMed:9784530"
FT MUTAGEN 254
FT /note="I->E: No effect on enzymatic activity or
FT cytotoxicity."
FT /evidence="ECO:0000269|PubMed:9784530"
FT MUTAGEN 255
FT /note="L->E: No effect on enzymatic activity or
FT cytotoxicity."
FT /evidence="ECO:0000269|PubMed:9784530"
FT MUTAGEN 256
FT /note="G->E: 225-fold decrease in cytotoxicity, probably
FT due to reduced translocation across the ER membrane; when
FT associated with D-253."
FT /evidence="ECO:0000269|PubMed:9784530"
FT MUTAGEN 256
FT /note="G->E: No effect on enzymatic activity; slight
FT decrease in cytotoxicity."
FT /evidence="ECO:0000269|PubMed:9784530"
FT MUTAGEN 299
FT /note="W->F,G: No effect on cytotoxicity."
FT /evidence="ECO:0000269|PubMed:7768810"
FT MUTAGEN 300
FT /note="D->K: Reduced subunit association and cytotoxicity."
FT /evidence="ECO:0000269|PubMed:7768810"
FT MUTAGEN 310
FT /note="R->E: Reduced subunit association and cytotoxicity."
FT /evidence="ECO:0000269|PubMed:7768810"
FT MUTAGEN 311
FT /note="R->E: Reduced subunit association and cytotoxicity."
FT /evidence="ECO:0000269|PubMed:7768810"
FT CONFLICT 190
FT /note="A -> P (in Ref. 2; CAA30741)"
FT /evidence="ECO:0000305"
FT STRAND 24..28
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 32..46
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 47..55
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 71..77
FT /evidence="ECO:0007829|PDB:1DM0"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:1DM0"
FT TURN 95..98
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:1DM0"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 154..165
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 174..192
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 194..201
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 216..222
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 225..231
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 239..243
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 251..257
FT /evidence="ECO:0007829|PDB:1DM0"
FT TURN 286..288
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 291..293
FT /evidence="ECO:0007829|PDB:1DM0"
FT STRAND 295..300
FT /evidence="ECO:0007829|PDB:1DM0"
FT HELIX 301..307
FT /evidence="ECO:0007829|PDB:1DM0"
SQ SEQUENCE 315 AA; 34814 MW; 8A423DF7ABF58F30 CRC64;
MKIIIFRVLT FFFVIFSVNV VAKEFTLDFS TAKTYVDSLN VIRSAIGTPL QTISSGGTSL
LMIDSGTGDN LFAVDVRGID PEEGRFNNLR LIVERNNLYV TGFVNRTNNV FYRFADFSHV
TFPGTTAVTL SGDSSYTTLQ RVAGISRTGM QINRHSLTTS YLDLMSHSGT SLTQSVARAM
LRFVTVTAEA LRFRQIQRGF RTTLDDLSGR SYVMTAEDVD LTLNWGRLSS VLPDYHGQDS
VRVGRISFGS INAILGSVAL ILNCHHHASR VARMASDEFP SMCPADGRVR GITHNKILWD
SSTLGAILMR RTISS
