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P00588

- DTX_CORBE

UniProt

P00588 - DTX_CORBE

Protein

Diphtheria toxin

Gene
N/A
Organism
Corynephage beta
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 98 (01 Oct 2014)
      Sequence version 2 (01 May 1991)
      Previous versions | rss
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    Functioni

    Diphtheria toxin, produced by a phage infecting Corynebacterium diphtheriae, is a proenzyme that, after activation, catalyzes the covalent attachment of the ADP ribose moiety of NAD to eukaryotic elongation factor 2 (eEF-2). Fragment A is the catalytic portion responsible for enzymatic ADP-ribosylation of elongation factor 2, while fragment B is responsible for binding of toxin to cell receptors and entry of fragment A.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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei53 – 531NAD
    Binding sitei97 – 971NAD
    Active sitei180 – 1801
    Sitei185 – 1851Modification inactivates enzyme

    GO - Molecular functioni

    1. NAD+-diphthamide ADP-ribosyltransferase activity Source: UniProtKB-EC

    GO - Biological processi

    1. pathogenesis Source: InterPro

    Keywords - Molecular functioni

    Glycosyltransferase, Toxin, Transferase

    Keywords - Ligandi

    NAD

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15583.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Diphtheria toxin
    Short name:
    DT
    Alternative name(s):
    NAD(+)--diphthamide ADP-ribosyltransferase (EC:2.4.2.36)
    Cleaved into the following 2 chains:
    OrganismiCorynephage beta
    Taxonomic identifieri10703 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stageCaudoviralesSiphoviridaeLambdalikevirusunclassified Lambda-like viruses
    Virus hostiCorynebacterium diphtheriae [TaxID: 1717]

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: InterPro

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi180 – 1801E → A: Loss of toxicity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 32321 PublicationAdd
    BLAST
    Chaini33 – 225193Diphtheria toxin fragment APRO_0000019345Add
    BLAST
    Chaini226 – 567342Diphtheria toxin fragment BPRO_0000019346Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi218 ↔ 233
    Disulfide bondi493 ↔ 503

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond

    Miscellaneous databases

    PMAP-CutDBP00588.

    Interactioni

    Subunit structurei

    Homodimer.

    Protein-protein interaction databases

    DIPiDIP-60031N.

    Structurei

    Secondary structure

    1
    567
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi34 – 374
    Helixi40 – 423
    Beta strandi44 – 474
    Beta strandi50 – 556
    Turni57 – 615
    Helixi62 – 654
    Beta strandi71 – 733
    Helixi80 – 823
    Beta strandi84 – 896
    Helixi91 – 955
    Beta strandi101 – 1033
    Turni104 – 1063
    Beta strandi111 – 1166
    Beta strandi118 – 12710
    Helixi131 – 1377
    Beta strandi142 – 1443
    Helixi146 – 1505
    Helixi153 – 1597
    Beta strandi160 – 1623
    Beta strandi164 – 1718
    Beta strandi179 – 1835
    Helixi187 – 1904
    Beta strandi192 – 1987
    Helixi199 – 2024
    Helixi208 – 2158
    Helixi216 – 2183
    Helixi238 – 25316
    Helixi256 – 2638
    Helixi272 – 28615
    Helixi290 – 2923
    Helixi293 – 2997
    Helixi303 – 3053
    Helixi307 – 32014
    Helixi323 – 3264
    Helixi329 – 3368
    Helixi342 – 3465
    Helixi358 – 37922
    Turni387 – 3904
    Helixi391 – 40717
    Beta strandi421 – 4233
    Beta strandi426 – 4327
    Helixi433 – 4364
    Beta strandi437 – 4393
    Beta strandi444 – 45714
    Beta strandi459 – 4613
    Beta strandi463 – 4675
    Turni470 – 4723
    Beta strandi473 – 4753
    Turni477 – 4793
    Beta strandi481 – 4844
    Beta strandi487 – 4893
    Beta strandi491 – 4966
    Turni497 – 4993
    Beta strandi500 – 5078
    Beta strandi509 – 5124
    Beta strandi517 – 5259
    Turni533 – 5353
    Beta strandi540 – 55011
    Beta strandi553 – 56210
    Beta strandi564 – 5663

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1DDTX-ray2.00A33-567[»]
    1DTPX-ray2.50A33-222[»]
    1F0LX-ray1.55A/B33-567[»]
    1MDTX-ray2.30A/B33-567[»]
    1SGKX-ray2.30A33-567[»]
    1TOXX-ray2.30A/B33-567[»]
    1XDTX-ray2.65T33-567[»]
    4AE0X-ray2.00A33-567[»]
    4AE1X-ray2.08A/B33-567[»]
    ProteinModelPortaliP00588.
    SMRiP00588. Positions 33-567.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP00588.

    Family & Domainsi

    Keywords - Domaini

    Signal

    Family and domain databases

    Gene3Di1.10.490.40. 1 hit.
    2.60.40.700. 1 hit.
    InterProiIPR000512. Diphtheria_toxin.
    IPR022406. Diphtheria_toxin_catalytic_dom.
    IPR022404. Diphtheria_toxin_rcpt-bd_dom.
    IPR022405. Diphtheria_toxin_translocation.
    [Graphical view]
    PfamiPF02763. Diphtheria_C. 1 hit.
    PF01324. Diphtheria_R. 1 hit.
    PF02764. Diphtheria_T. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000490. Diphtheria_toxin. 1 hit.
    PRINTSiPR00769. DPTHRIATOXIN.
    SUPFAMiSSF49380. SSF49380. 1 hit.
    SSF56845. SSF56845. 1 hit.

    Sequencei

    Sequence statusi: Complete.

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

    P00588-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLVRGYVVSR KLFASILIGA LLGIGAPPSA HAGADDVVDS SKSFVMENFS    50
    SYHGTKPGYV DSIQKGIQKP KSGTQGNYDD DWKGFYSTDN KYDAAGYSVD 100
    NENPLSGKAG GVVKVTYPGL TKVLALKVDN AETIKKELGL SLTEPLMEQV 150
    GTEEFIKRFG DGASRVVLSL PFAEGSSSVE YINNWEQAKA LSVELEINFE 200
    TRGKRGQDAM YEYMAQACAG NRVRRSVGSS LSCINLDWDV IRDKTKTKIE 250
    SLKEHGPIKN KMSESPNKTV SEEKAKQYLE EFHQTALEHP ELSELKTVTG 300
    TNPVFAGANY AAWAVNVAQV IDSETADNLE KTTAALSILP GIGSVMGIAD 350
    GAVHHNTEEI VAQSIALSSL MVAQAIPLVG ELVDIGFAAY NFVESIINLF 400
    QVVHNSYNRP AYSPGHKTQP FLHDGYAVSW NTVEDSIIRT GFQGESGHDI 450
    KITAENTPLP IAGVLLPTIP GKLDVNKSKT HISVNGRKIR MRCRAIDGDV 500
    TFCRPKSPVY VGNGVHANLH VAFHRSSSEK IHSNEISSDS IGVLGYQKTV 550
    DHTKVNSKLS LFFEIKS 567
    Length:567
    Mass (Da):61,602
    Last modified:May 1, 1991 - v2
    Checksum:iCAF82A75EA693FF8
    GO

    Sequence cautioni

    The sequence AAA32182.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti178 – 1803SVE → VES AA sequence (PubMed:221484)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01722 Genomic DNA. Translation: AAA32182.1. Different initiation.
    X00703 Genomic DNA. Translation: CAA25302.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01722 Genomic DNA. Translation: AAA32182.1 . Different initiation.
    X00703 Genomic DNA. Translation: CAA25302.1 .

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1DDT X-ray 2.00 A 33-567 [» ]
    1DTP X-ray 2.50 A 33-222 [» ]
    1F0L X-ray 1.55 A/B 33-567 [» ]
    1MDT X-ray 2.30 A/B 33-567 [» ]
    1SGK X-ray 2.30 A 33-567 [» ]
    1TOX X-ray 2.30 A/B 33-567 [» ]
    1XDT X-ray 2.65 T 33-567 [» ]
    4AE0 X-ray 2.00 A 33-567 [» ]
    4AE1 X-ray 2.08 A/B 33-567 [» ]
    ProteinModelPortali P00588.
    SMRi P00588. Positions 33-567.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-60031N.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Enzyme and pathway databases

    BioCyci MetaCyc:MONOMER-15583.

    Miscellaneous databases

    EvolutionaryTracei P00588.
    PMAP-CutDB P00588.

    Family and domain databases

    Gene3Di 1.10.490.40. 1 hit.
    2.60.40.700. 1 hit.
    InterProi IPR000512. Diphtheria_toxin.
    IPR022406. Diphtheria_toxin_catalytic_dom.
    IPR022404. Diphtheria_toxin_rcpt-bd_dom.
    IPR022405. Diphtheria_toxin_translocation.
    [Graphical view ]
    Pfami PF02763. Diphtheria_C. 1 hit.
    PF01324. Diphtheria_R. 1 hit.
    PF02764. Diphtheria_T. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000490. Diphtheria_toxin. 1 hit.
    PRINTSi PR00769. DPTHRIATOXIN.
    SUPFAMi SSF49380. SSF49380. 1 hit.
    SSF56845. SSF56845. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Nucleotide sequence of the structural gene for diphtheria toxin carried by corynebacteriophage beta."
      Greenfield L., Bjorn M.J., Horn G., Fong D., Buck G.A., Collier R.J., Kaplan D.A.
      Proc. Natl. Acad. Sci. U.S.A. 80:6853-6857(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The amino acid sequence of fragment A, an enzymically active fragment of diphtheria toxin. III. The chymotryptic peptides, the peptides derived by cleavage at tryptophan residues, and the complete sequence of the protein."
      Delange R.J., Williams L.C., Drazin R.E., Collier R.J.
      J. Biol. Chem. 254:5838-5842(1979) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 33-225.
    3. "Occurrence of tryptophan in the enzymically active site of diphtheria toxin fragment A."
      Michel A., Dirkx J.
      Biochim. Biophys. Acta 491:286-295(1977) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVE SITE TRP-185.
    4. "Tyrosine 65 is photolabeled by 8-azidoadenine and 8-azidoadenosine at the NAD binding site of diphtheria toxin."
      Papini E., Santucci A., Schiavo G., Domenighini M., Neri P., Rappuoli R., Montecucco C.
      J. Biol. Chem. 266:2494-2498(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVE SITE TYR-97.
    5. Cited for: FUNCTION AS AN ADP-RIBOSYLTRANSFERASE.
    6. Cited for: FUNCTION AS A TOXIN, FUNCTION AS AN ADP-RIBOSYLTRANSFERASE, ENZYME REGULATION, EXPRESSION IN YEAST, MUTAGENESIS OF GLU-180.
    7. Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
    8. "Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide."
      Bell C.E., Eisenberg D.
      Biochemistry 35:1137-1149(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
    9. "Crystal structure of nucleotide-free diphtheria toxin."
      Bell C.E., Eisenberg D.
      Biochemistry 36:481-488(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
    10. "Crystal structure of the complex of diphtheria toxin with an extracellular fragment of its receptor."
      Louie G.V., Yang W., Bowman M.E., Choe S.
      Mol. Cell 1:67-78(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF COMPLEX WITH RECEPTOR.

    Entry informationi

    Entry nameiDTX_CORBE
    AccessioniPrimary (citable) accession number: P00588
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: May 1, 1991
    Last modified: October 1, 2014
    This is version 98 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Direct protein sequencing

    Documents

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

    External Data

    Dasty 3