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Protein

Cholix toxin

Gene

chxA

Organism
Vibrio cholerae
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

An NAD-dependent ADP-ribosyltransferase (ADPRT), it catalyzes the transfer of the ADP-ribosyl moiety of oxidized NAD onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. It probably uses the eukaryotic prolow-density lipoprotein receptor-related protein 1 (LRP1) to enter mouse cells, although there seems to be at least one other receptor as well. Is active against mouse fibroblasts, Chinese hamster ovary eEF-2, brine shrimp (Artemia spp. nauplii) and upon expression in S.cerevisiae.2 Publications

Catalytic activityi

NAD+ + diphthamide-[translation elongation factor 2] = nicotinamide + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2].

Enzyme regulationi

Partially inhibited by 1,8-naphthalimide (NAP).1 Publication

Kineticsi

For ADP-ribosyltransferase activity of a catalytic fragment of residues 459-666.

  1. KM=45 µM for NAD1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei613 – 6131Curated

    GO - Molecular functioni

    Complete GO annotation...

    Keywords - Molecular functioni

    Glycosyltransferase, Toxin, Transferase

    Keywords - Ligandi

    NAD

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cholix toxin (EC:2.4.2.36)
    Alternative name(s):
    Exotoxin A
    NAD(+)--diphthamide ADP-ribosyltransferase
    Gene namesi
    Name:chxA
    Synonyms:toxA
    OrganismiVibrio cholerae
    Taxonomic identifieri666 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaVibrionalesVibrionaceaeVibrio

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi606 – 6061E → A: Loss of ADPRT activity, loss of toxicity against yeast. 1 Publication
    Mutagenesisi613 – 6131E → A: Loss of ADPRT activity, loss of toxicity against mouse cells, brine shrimp and yeast. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3232Sequence AnalysisAdd
    BLAST
    Chaini33 – 666634Cholix toxinPRO_0000409819Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi43 ↔ 47
    Disulfide bondi240 ↔ 257
    Disulfide bondi310 ↔ 332
    Disulfide bondi426 ↔ 433

    Post-translational modificationi

    Probably requires further proteolytic processing to generate a fragment with toxic activity.

    Keywords - PTMi

    Disulfide bond

    Structurei

    Secondary structure

    1
    666
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi39 – 424Combined sources
    Beta strandi47 – 493Combined sources
    Beta strandi57 – 626Combined sources
    Beta strandi71 – 8111Combined sources
    Beta strandi94 – 996Combined sources
    Turni100 – 1023Combined sources
    Beta strandi103 – 1086Combined sources
    Beta strandi113 – 1153Combined sources
    Beta strandi120 – 1267Combined sources
    Beta strandi131 – 1377Combined sources
    Beta strandi139 – 15214Combined sources
    Beta strandi157 – 16610Combined sources
    Beta strandi170 – 1723Combined sources
    Beta strandi177 – 1826Combined sources
    Helixi185 – 1906Combined sources
    Turni191 – 1933Combined sources
    Beta strandi194 – 20310Combined sources
    Beta strandi208 – 21912Combined sources
    Helixi226 – 2305Combined sources
    Helixi231 – 2344Combined sources
    Helixi236 – 2416Combined sources
    Helixi245 – 2484Combined sources
    Beta strandi269 – 2735Combined sources
    Beta strandi289 – 2935Combined sources
    Helixi300 – 31011Combined sources
    Helixi314 – 3174Combined sources
    Helixi328 – 34619Combined sources
    Helixi350 – 3545Combined sources
    Helixi355 – 3584Combined sources
    Helixi361 – 3633Combined sources
    Helixi366 – 38116Combined sources
    Helixi385 – 40319Combined sources
    Helixi409 – 41810Combined sources
    Beta strandi420 – 4256Combined sources
    Beta strandi441 – 4455Combined sources
    Helixi450 – 4534Combined sources
    Beta strandi460 – 4623Combined sources
    Beta strandi465 – 4684Combined sources
    Helixi471 – 48313Combined sources
    Beta strandi486 – 4949Combined sources
    Helixi496 – 5049Combined sources
    Helixi516 – 5205Combined sources
    Beta strandi523 – 5297Combined sources
    Helixi530 – 5345Combined sources
    Helixi545 – 5473Combined sources
    Helixi551 – 5555Combined sources
    Beta strandi559 – 5668Combined sources
    Helixi567 – 5726Combined sources
    Beta strandi573 – 5753Combined sources
    Helixi580 – 5823Combined sources
    Helixi584 – 5918Combined sources
    Beta strandi601 – 6077Combined sources
    Beta strandi612 – 6165Combined sources
    Helixi618 – 6214Combined sources
    Beta strandi625 – 6328Combined sources
    Helixi643 – 6497Combined sources
    Helixi650 – 6523Combined sources
    Helixi662 – 6643Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2Q5TX-ray2.10A33-666[»]
    2Q6MX-ray1.25A459-666[»]
    3ESSX-ray1.19A459-665[»]
    3KI0X-ray1.29A459-665[»]
    3KI1X-ray1.43A459-665[»]
    3KI2X-ray1.28A459-665[»]
    3KI3X-ray1.27A459-665[»]
    3KI4X-ray1.65A459-665[»]
    3KI5X-ray1.55A459-665[»]
    3KI6X-ray1.54A459-665[»]
    3KI7X-ray1.32A459-665[»]
    3NY6X-ray1.68A459-665[»]
    3Q9OX-ray1.79A33-666[»]
    ProteinModelPortaliQ5EK40.
    SMRiQ5EK40. Positions 37-662.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ5EK40.

    Family & Domainsi

    Keywords - Domaini

    Signal

    Family and domain databases

    Gene3Di2.60.120.200. 1 hit.
    3.90.1350.10. 1 hit.
    InterProiIPR013320. ConA-like_dom.
    IPR015185. Exotox-A_bind.
    IPR015099. Exotox-A_cataly_dom.
    IPR015186. Exotox-A_middle_dom.
    [Graphical view]
    PfamiPF09101. Exotox-A_bind. 1 hit.
    PF09009. Exotox-A_cataly. 1 hit.
    PF09102. Exotox-A_target. 1 hit.
    [Graphical view]
    SUPFAMiSSF49899. SSF49899. 1 hit.
    SSF56864. SSF56864. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q5EK40-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MYLTFYLEKV MKKMLLIAGA TVISSMAHPT FAVEDELNIF DECRSPCSLT
    60 70 80 90 100
    PEPGKPIQSK LSIPSDVVLD EGVLYYSMTI NDEQNDIKDE DKGESIITIG
    110 120 130 140 150
    EFATVRATRH YVNQDAPFGV IHLDITTENG TKTYSYNRKE GEFAINWLVP
    160 170 180 190 200
    IGEDSPASIK ISVDELDQQR NIIEVPKLYS IDLDNQTLEQ WKTQGNVSFS
    210 220 230 240 250
    VTRPEHNIAI SWPSVSYKAA QKEGSRHKRW AHWHTGLALC WLVPMDAIYN
    260 270 280 290 300
    YITQQNCTLG DNWFGGSYET VAGTPKVITV KQGIEQKPVE QRIHFSKGNA
    310 320 330 340 350
    MSALAAHRVC GVPLETLARS RKPRDLTDDL SCAYQAQNIV SLFVATRILF
    360 370 380 390 400
    SHLDSVFTLN LDEQEPEVAE RLSDLRRINE NNPGMVTQVL TVARQIYNDY
    410 420 430 440 450
    VTHHPGLTPE QTSAGAQAAD ILSLFCPDAD KSCVASNNDQ ANINIESRSG
    460 470 480 490 500
    RSYLPENRAV ITPQGVTNWT YQELEATHQA LTREGYVFVG YHGTNHVAAQ
    510 520 530 540 550
    TIVNRIAPVP RGNNTENEEK WGGLYVATHA EVAHGYARIK EGTGEYGLPT
    560 570 580 590 600
    RAERDARGVM LRVYIPRASL ERFYRTNTPL ENAEEHITQV IGHSLPLRNE
    610 620 630 640 650
    AFTGPESAGG EDETVIGWDM AIHAVAIPST IPGNAYEELA IDEEAVAKEQ
    660
    SISTKPPYKE RKDELK
    Length:666
    Mass (Da):74,293
    Last modified:March 15, 2005 - v1
    Checksum:i3A76A86E0BC7FDD7
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY876053 Genomic DNA. Translation: AAW80252.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY876053 Genomic DNA. Translation: AAW80252.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2Q5TX-ray2.10A33-666[»]
    2Q6MX-ray1.25A459-666[»]
    3ESSX-ray1.19A459-665[»]
    3KI0X-ray1.29A459-665[»]
    3KI1X-ray1.43A459-665[»]
    3KI2X-ray1.28A459-665[»]
    3KI3X-ray1.27A459-665[»]
    3KI4X-ray1.65A459-665[»]
    3KI5X-ray1.55A459-665[»]
    3KI6X-ray1.54A459-665[»]
    3KI7X-ray1.32A459-665[»]
    3NY6X-ray1.68A459-665[»]
    3Q9OX-ray1.79A33-666[»]
    ProteinModelPortaliQ5EK40.
    SMRiQ5EK40. Positions 37-662.
    ModBaseiSearch...
    MobiDBiSearch...

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ5EK40.

    Family and domain databases

    Gene3Di2.60.120.200. 1 hit.
    3.90.1350.10. 1 hit.
    InterProiIPR013320. ConA-like_dom.
    IPR015185. Exotox-A_bind.
    IPR015099. Exotox-A_cataly_dom.
    IPR015186. Exotox-A_middle_dom.
    [Graphical view]
    PfamiPF09101. Exotox-A_bind. 1 hit.
    PF09009. Exotox-A_cataly. 1 hit.
    PF09102. Exotox-A_target. 1 hit.
    [Graphical view]
    SUPFAMiSSF49899. SSF49899. 1 hit.
    SSF56864. SSF56864. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    1. "A glimpse into the expanded genome content of Vibrio cholerae through identification of genes present in environmental strains."
      Purdy A., Rohwer F., Edwards R., Azam F., Bartlett D.H.
      J. Bacteriol. 187:2992-3001(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: TP.
    2. Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 459-666 IN COMPLEX WITH INHIBITOR AND (2.1 ANGSTROMS) OF 33-666, FUNCTION AS A TOXIN, FUNCTION AS A GLYCOHYDROLASE, FUNCTION AS AN ADP-RIBOSYLTRANSFERASE, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-613.
      Strain: TP.
    3. Cited for: X-RAY CRYSTALLOGRAPHY (1.19 ANGSTROMS) OF 459-665 IN COMPLEX WITH INHIBITOR, FUNCTION AS A TOXIN, ENZYME REGULATION, MUTAGENESIS OF GLU-606.
      Strain: TP.
    4. "Newly discovered and characterized antivirulence compounds inhibit bacterial mono-ADP-ribosyltransferase toxins."
      Turgeon Z., Jorgensen R., Visschedyk D., Edwards P.R., Legree S., McGregor C., Fieldhouse R.J., Mangroo D., Schapira M., Merrill A.R.
      Antimicrob. Agents Chemother. 55:983-991(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.27 ANGSTROMS) OF 459-665 IN COMPLEX WITH INHIBITORS.
      Strain: TP.

    Entry informationi

    Entry nameiCHXA_VIBCL
    AccessioniPrimary (citable) accession number: Q5EK40
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 28, 2011
    Last sequence update: March 15, 2005
    Last modified: November 26, 2014
    This is version 46 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Exotoxins are often highly strain specific; not encoded in strain ATCC 39315 / El Tor Inabe N16961.

    Keywords - Technical termi

    3D-structure

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.