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P00588

- DTX_CORBE

UniProt

P00588 - DTX_CORBE

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Protein

Diphtheria toxin

Gene
N/A
Organism
Corynephage beta
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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
Complete GO annotation...

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
Complete GO annotation...

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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

        10         20         30         40         50
MLVRGYVVSR KLFASILIGA LLGIGAPPSA HAGADDVVDS SKSFVMENFS
60 70 80 90 100
SYHGTKPGYV DSIQKGIQKP KSGTQGNYDD DWKGFYSTDN KYDAAGYSVD
110 120 130 140 150
NENPLSGKAG GVVKVTYPGL TKVLALKVDN AETIKKELGL SLTEPLMEQV
160 170 180 190 200
GTEEFIKRFG DGASRVVLSL PFAEGSSSVE YINNWEQAKA LSVELEINFE
210 220 230 240 250
TRGKRGQDAM YEYMAQACAG NRVRRSVGSS LSCINLDWDV IRDKTKTKIE
260 270 280 290 300
SLKEHGPIKN KMSESPNKTV SEEKAKQYLE EFHQTALEHP ELSELKTVTG
310 320 330 340 350
TNPVFAGANY AAWAVNVAQV IDSETADNLE KTTAALSILP GIGSVMGIAD
360 370 380 390 400
GAVHHNTEEI VAQSIALSSL MVAQAIPLVG ELVDIGFAAY NFVESIINLF
410 420 430 440 450
QVVHNSYNRP AYSPGHKTQP FLHDGYAVSW NTVEDSIIRT GFQGESGHDI
460 470 480 490 500
KITAENTPLP IAGVLLPTIP GKLDVNKSKT HISVNGRKIR MRCRAIDGDV
510 520 530 540 550
TFCRPKSPVY VGNGVHANLH VAFHRSSSEK IHSNEISSDS IGVLGYQKTV
560
DHTKVNSKLS LFFEIKS
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.Curated

Experimental Info

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K01722 Genomic DNA. Translation: AAA32182.1. Different initiation.
X00703 Genomic DNA. Translation: CAA25302.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K01722 Genomic DNA. Translation: AAA32182.1 . Different initiation.
X00703 Genomic DNA. Translation: CAA25302.1 .

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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: November 26, 2014
This is version 99 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