CHXA_VIBCL
ID CHXA_VIBCL Reviewed; 666 AA.
AC Q5EK40;
DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Cholix toxin;
DE EC=2.4.2.36;
DE AltName: Full=Exotoxin A;
DE AltName: Full=NAD(+)--diphthamide ADP-ribosyltransferase;
DE Flags: Precursor;
GN Name=chxA; Synonyms=toxA;
OS Vibrio cholerae.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=666;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=TP;
RX PubMed=15838025; DOI=10.1128/jb.187.9.2992-3001.2005;
RA Purdy A., Rohwer F., Edwards R., Azam F., Bartlett D.H.;
RT "A glimpse into the expanded genome content of Vibrio cholerae through
RT identification of genes present in environmental strains.";
RL J. Bacteriol. 187:2992-3001(2005).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 459-666 IN COMPLEX WITH INHIBITOR
RP AND (2.1 ANGSTROMS) OF 33-666, FUNCTION AS A TOXIN, FUNCTION AS A
RP GLYCOHYDROLASE, FUNCTION AS AN ADP-RIBOSYLTRANSFERASE, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF GLU-613.
RC STRAIN=TP;
RX PubMed=18276581; DOI=10.1074/jbc.m710008200;
RA Jorgensen R., Purdy A.E., Fieldhouse R.J., Kimber M.S., Bartlett D.H.,
RA Merrill A.R.;
RT "Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae.";
RL J. Biol. Chem. 283:10671-10678(2008).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.19 ANGSTROMS) OF 459-665 IN COMPLEX WITH
RP INHIBITOR, FUNCTION AS A TOXIN, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP GLU-606.
RC STRAIN=TP;
RX PubMed=19793133; DOI=10.1111/j.1574-6968.2009.01777.x;
RA Turgeon Z., White D., Jorgensen R., Visschedyk D., Fieldhouse R.J.,
RA Mangroo D., Merrill A.R.;
RT "Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins.";
RL FEMS Microbiol. Lett. 300:97-106(2009).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.27 ANGSTROMS) OF 459-665 IN COMPLEX WITH
RP INHIBITORS.
RC STRAIN=TP;
RX PubMed=21135177; DOI=10.1128/aac.01164-10;
RA Turgeon Z., Jorgensen R., Visschedyk D., Edwards P.R., Legree S.,
RA McGregor C., Fieldhouse R.J., Mangroo D., Schapira M., Merrill A.R.;
RT "Newly discovered and characterized antivirulence compounds inhibit
RT bacterial mono-ADP-ribosyltransferase toxins.";
RL Antimicrob. Agents Chemother. 55:983-991(2011).
CC -!- FUNCTION: An NAD-dependent ADP-ribosyltransferase (ADPRT), it catalyzes
CC the transfer of the ADP-ribosyl moiety of oxidized NAD onto eukaryotic
CC elongation factor 2 (eEF-2) thus arresting protein synthesis. It
CC probably uses the eukaryotic prolow-density lipoprotein receptor-
CC related protein 1 (LRP1) to enter mouse cells, although there seems to
CC be at least one other receptor as well. Is active against mouse
CC fibroblasts, Chinese hamster ovary eEF-2, brine shrimp (Artemia spp.
CC nauplii) and upon expression in S.cerevisiae.
CC {ECO:0000269|PubMed:18276581, ECO:0000269|PubMed:19793133}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphthamide-[translation elongation factor 2] + NAD(+) = H(+)
CC + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2] +
CC nicotinamide; Xref=Rhea:RHEA:11820, Rhea:RHEA-COMP:10174, Rhea:RHEA-
CC COMP:10175, ChEBI:CHEBI:15378, ChEBI:CHEBI:16692, ChEBI:CHEBI:17154,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:82697; EC=2.4.2.36;
CC -!- ACTIVITY REGULATION: Partially inhibited by 1,8-naphthalimide (NAP).
CC {ECO:0000269|PubMed:19793133}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=45 uM for NAD {ECO:0000269|PubMed:18276581};
CC Note=For ADP-ribosyltransferase activity of a catalytic fragment of
CC residues 459-666.;
CC -!- PTM: Probably requires further proteolytic processing to generate a
CC fragment with toxic activity.
CC -!- MISCELLANEOUS: Exotoxins are often highly strain specific; not encoded
CC in strain ATCC 39315 / El Tor Inabe N16961.
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DR EMBL; AY876053; AAW80252.1; -; Genomic_DNA.
DR PDB; 2Q5T; X-ray; 2.10 A; A=33-666.
DR PDB; 2Q6M; X-ray; 1.25 A; A=459-666.
DR PDB; 3ESS; X-ray; 1.19 A; A=459-665.
DR PDB; 3KI0; X-ray; 1.29 A; A=459-665.
DR PDB; 3KI1; X-ray; 1.43 A; A=459-665.
DR PDB; 3KI2; X-ray; 1.28 A; A=459-665.
DR PDB; 3KI3; X-ray; 1.27 A; A=459-665.
DR PDB; 3KI4; X-ray; 1.65 A; A=459-665.
DR PDB; 3KI5; X-ray; 1.55 A; A=459-665.
DR PDB; 3KI6; X-ray; 1.54 A; A=459-665.
DR PDB; 3KI7; X-ray; 1.32 A; A=459-665.
DR PDB; 3NY6; X-ray; 1.68 A; A=459-665.
DR PDB; 3Q9O; X-ray; 1.79 A; A=33-666.
DR PDBsum; 2Q5T; -.
DR PDBsum; 2Q6M; -.
DR PDBsum; 3ESS; -.
DR PDBsum; 3KI0; -.
DR PDBsum; 3KI1; -.
DR PDBsum; 3KI2; -.
DR PDBsum; 3KI3; -.
DR PDBsum; 3KI4; -.
DR PDBsum; 3KI5; -.
DR PDBsum; 3KI6; -.
DR PDBsum; 3KI7; -.
DR PDBsum; 3NY6; -.
DR PDBsum; 3Q9O; -.
DR AlphaFoldDB; Q5EK40; -.
DR SMR; Q5EK40; -.
DR DrugBank; DB08348; N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDE.
DR TCDB; 1.C.73.1.2; the pseudomonas exotoxin a (p-exoa) family.
DR BRENDA; 2.4.2.31; 6626.
DR BRENDA; 2.4.2.36; 6626.
DR EvolutionaryTrace; Q5EK40; -.
DR GO; GO:0047286; F:NAD+-diphthamide ADP-ribosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR CDD; cd01436; Dipth_tox_like; 1.
DR Gene3D; 3.90.1350.10; -; 1.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR015185; Exotox-A_bind.
DR InterPro; IPR015099; Exotox-A_cataly_dom.
DR InterPro; IPR015186; Exotox-A_middle_dom.
DR InterPro; IPR036478; Exotox-A_middle_dom_sf.
DR Pfam; PF09101; Exotox-A_bind; 1.
DR Pfam; PF09009; Exotox-A_cataly; 1.
DR Pfam; PF09102; Exotox-A_target; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF56864; SSF56864; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycosyltransferase; NAD;
KW Nucleotidyltransferase; Signal; Toxin; Transferase; Virulence.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..666
FT /note="Cholix toxin"
FT /id="PRO_0000409819"
FT REGION 645..666
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 613
FT /evidence="ECO:0000305"
FT DISULFID 43..47
FT DISULFID 240..257
FT DISULFID 310..332
FT DISULFID 426..433
FT MUTAGEN 606
FT /note="E->A: Loss of ADPRT activity, loss of toxicity
FT against yeast."
FT /evidence="ECO:0000269|PubMed:19793133"
FT MUTAGEN 613
FT /note="E->A: Loss of ADPRT activity, loss of toxicity
FT against mouse cells, brine shrimp and yeast."
FT /evidence="ECO:0000269|PubMed:18276581"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 71..81
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:3Q9O"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 103..108
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:2Q5T"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 131..137
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 139..152
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 157..166
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 185..190
FT /evidence="ECO:0007829|PDB:3Q9O"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 194..203
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 208..219
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 226..230
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 236..241
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 245..248
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 300..310
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 314..317
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 328..346
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 350..354
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 361..363
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 366..381
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 385..403
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 409..418
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 420..425
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 441..445
FT /evidence="ECO:0007829|PDB:3Q9O"
FT HELIX 450..453
FT /evidence="ECO:0007829|PDB:3Q9O"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:3ESS"
FT STRAND 465..468
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 471..483
FT /evidence="ECO:0007829|PDB:3ESS"
FT STRAND 486..494
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 496..504
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 516..520
FT /evidence="ECO:0007829|PDB:2Q6M"
FT STRAND 523..529
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 530..534
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 545..547
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 551..555
FT /evidence="ECO:0007829|PDB:3ESS"
FT STRAND 559..566
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 567..572
FT /evidence="ECO:0007829|PDB:3ESS"
FT STRAND 573..575
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 580..582
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 584..591
FT /evidence="ECO:0007829|PDB:3ESS"
FT STRAND 601..607
FT /evidence="ECO:0007829|PDB:3ESS"
FT STRAND 612..616
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 618..621
FT /evidence="ECO:0007829|PDB:3ESS"
FT STRAND 625..632
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 643..649
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 650..652
FT /evidence="ECO:0007829|PDB:3ESS"
FT HELIX 662..664
FT /evidence="ECO:0007829|PDB:3ESS"
SQ SEQUENCE 666 AA; 74293 MW; 3A76A86E0BC7FDD7 CRC64;
MYLTFYLEKV MKKMLLIAGA TVISSMAHPT FAVEDELNIF DECRSPCSLT PEPGKPIQSK
LSIPSDVVLD EGVLYYSMTI NDEQNDIKDE DKGESIITIG EFATVRATRH YVNQDAPFGV
IHLDITTENG TKTYSYNRKE GEFAINWLVP IGEDSPASIK ISVDELDQQR NIIEVPKLYS
IDLDNQTLEQ WKTQGNVSFS VTRPEHNIAI SWPSVSYKAA QKEGSRHKRW AHWHTGLALC
WLVPMDAIYN YITQQNCTLG DNWFGGSYET VAGTPKVITV KQGIEQKPVE QRIHFSKGNA
MSALAAHRVC GVPLETLARS RKPRDLTDDL SCAYQAQNIV SLFVATRILF SHLDSVFTLN
LDEQEPEVAE RLSDLRRINE NNPGMVTQVL TVARQIYNDY VTHHPGLTPE QTSAGAQAAD
ILSLFCPDAD KSCVASNNDQ ANINIESRSG RSYLPENRAV ITPQGVTNWT YQELEATHQA
LTREGYVFVG YHGTNHVAAQ TIVNRIAPVP RGNNTENEEK WGGLYVATHA EVAHGYARIK
EGTGEYGLPT RAERDARGVM LRVYIPRASL ERFYRTNTPL ENAEEHITQV IGHSLPLRNE
AFTGPESAGG EDETVIGWDM AIHAVAIPST IPGNAYEELA IDEEAVAKEQ SISTKPPYKE
RKDELK
