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P11439

- TOXA_PSEAE

UniProt

P11439 - TOXA_PSEAE

Protein

Exotoxin A

Gene

eta

Organism
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 2 (11 Jan 2001)
      Previous versions | rss
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    Functioni

    An NAD-dependent ADP-ribosyltransferase (ADPRT). Catalyzes the transfer of the ADP ribosyl moiety of oxidized NAD (NAD+) onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. Has an LD50 of 65 ng/ml against the human lung epithelial cell line C38.1 Publication

    Catalytic activityi

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

    Enzyme regulationi

    Inhibited by 1,8-naphthalimide (NAP) as well as a number of poly(ADP-ribose) polymerase inhibitors and other compounds.1 Publication

    Kineticsi

    For ADP-ribosyltransferase activity of the catalytic fragment 399-605.

    1. KM=121 µM for NAD

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei474 – 4741NAD1 Publication
    Active sitei578 – 57811 Publication
    Binding sitei578 – 5781NAD1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi465 – 4673NAD1 Publication
    Nucleotide bindingi479 – 4857NAD1 Publication

    GO - Molecular functioni

    1. NAD+-diphthamide ADP-ribosyltransferase activity Source: CACAO

    GO - Biological processi

    1. metabolic process Source: GOC

    Keywords - Molecular functioni

    Glycosyltransferase, Toxin, Transferase

    Keywords - Ligandi

    NAD

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15587.
    SABIO-RKP11439.

    Protein family/group databases

    TCDBi1.C.73.1.1. the pseudomonas exotoxin a (p-exoa) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Exotoxin A (EC:2.4.2.36)
    Short name:
    ETA
    Alternative name(s):
    NAD(+)--diphthamide ADP-ribosyltransferase
    PE
    Gene namesi
    Name:eta
    Ordered Locus Names:PA1148
    OrganismiPseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
    Taxonomic identifieri208964 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaPseudomonadalesPseudomonadaceaePseudomonas
    ProteomesiUP000002438: Chromosome

    Organism-specific databases

    PseudoCAPiPA1148.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi82 – 821K → E: Loss of toxicity, no binding to LRP1 receptor. 1 Publication
    Mutagenesisi481 – 4811R → H: 52-fold decrease in ADPRT activity, 55-fold reduction in GH activity, 31-fold increase in dissociation constant for NAD(+). 1 Publication
    Mutagenesisi571 – 5711E → A: 833-fold decrease in ADPRT activity, 4-fold reduction in GH activity, 2-fold increase in dissociation constant for NAD(+). 1 Publication
    Mutagenesisi576 – 5761R → A: 2-fold decrease in ADPRT activity, 14-fold reduction in GH activity, 3-fold increase in dissociation constant for NAD(+). 1 Publication
    Mutagenesisi578 – 5781E → A: 666-fold decrease in ADPRT activity, 14-fold reduction in GH activity, 2-fold increase in dissociation constant for NAD(+), loss of toxicity against mouse cells. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 25251 PublicationAdd
    BLAST
    Chaini26 – 638613Exotoxin APRO_0000019365Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi290 ↔ 3121 Publication

    Post-translational modificationi

    The 8 cysteines participate in intrachain disulfide bonds.

    Keywords - PTMi

    Disulfide bond

    Interactioni

    Protein-protein interaction databases

    STRINGi208964.PA1148.

    Structurei

    Secondary structure

    1
    638
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi32 – 354
    Beta strandi36 – 438
    Beta strandi49 – 546
    Helixi57 – 604
    Beta strandi63 – 7412
    Turni76 – 794
    Beta strandi80 – 856
    Turni86 – 883
    Beta strandi89 – 935
    Beta strandi95 – 1028
    Beta strandi106 – 1083
    Beta strandi110 – 1156
    Beta strandi117 – 1204
    Beta strandi122 – 13110
    Beta strandi136 – 14510
    Beta strandi151 – 1544
    Beta strandi157 – 1615
    Helixi164 – 1707
    Beta strandi173 – 1808
    Beta strandi189 – 20113
    Helixi213 – 2164
    Helixi218 – 2236
    Helixi225 – 2273
    Helixi230 – 2356
    Helixi243 – 2464
    Beta strandi249 – 2557
    Beta strandi270 – 2734
    Helixi280 – 29011
    Helixi294 – 2985
    Helixi307 – 3115
    Helixi313 – 32513
    Helixi330 – 3323
    Helixi333 – 34210
    Turni344 – 3474
    Helixi348 – 3569
    Helixi358 – 37619
    Helixi384 – 3874
    Beta strandi392 – 3965
    Beta strandi399 – 4035
    Helixi408 – 4103
    Beta strandi413 – 4186
    Helixi422 – 4243
    Beta strandi428 – 4303
    Beta strandi433 – 4353
    Beta strandi438 – 4403
    Helixi444 – 45613
    Beta strandi459 – 4679
    Helixi469 – 4779
    Helixi489 – 4913
    Beta strandi493 – 4997
    Helixi500 – 5045
    Beta strandi522 – 5298
    Helixi530 – 5356
    Beta strandi536 – 5383
    Beta strandi543 – 5453
    Helixi548 – 5569
    Beta strandi558 – 5614
    Beta strandi566 – 5727
    Beta strandi577 – 5815
    Helixi583 – 5875
    Beta strandi590 – 5934
    Helixi609 – 6113
    Helixi614 – 6174
    Beta strandi626 – 6283

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AERX-ray2.30A/B425-634[»]
    1DMAX-ray2.50A/B425-638[»]
    1IKPX-ray1.45A26-638[»]
    1IKQX-ray1.62A26-638[»]
    1XK9X-ray2.10A/B424-638[»]
    1ZM2X-ray3.07B/D/F424-630[»]
    1ZM3X-ray3.07B/D/F424-630[»]
    1ZM4X-ray2.90B/D/F424-630[»]
    1ZM9X-ray2.80B/D/F424-630[»]
    2ZITX-ray3.00B/D/F425-630[»]
    3B78X-ray2.50B/D/F425-630[»]
    3B82X-ray2.35B/D/F425-630[»]
    3B8HX-ray2.50B/D/F425-630[»]
    ProteinModelPortaliP11439.
    SMRiP11439. Positions 27-631.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11439.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni26 – 277252IA (required for target cell recognition)Add
    BLAST
    Regioni278 – 389112II (required for translocation in target cell cytoplasm)Add
    BLAST
    Regioni390 – 42940IBAdd
    BLAST
    Regioni430 – 638209III (required for ADP-ribosyl activity)Add
    BLAST

    Keywords - Domaini

    Signal

    Phylogenomic databases

    HOGENOMiHOG000081585.
    KOiK11020.
    OMAiAHESNEM.
    OrthoDBiEOG6ZPSVM.

    Family and domain databases

    Gene3Di2.60.120.200. 1 hit.
    3.90.1350.10. 1 hit.
    InterProiIPR008985. ConA-like_lec_gl_sf.
    IPR013320. ConA-like_subgrp.
    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.

    P11439-1 [UniParc]FASTAAdd to Basket

    « Hide

    MHLTPHWIPL VASLGLLAGG SFASAAEEAF DLWNECAKAC VLDLKDGVRS    50
    SRMSVDPAIA DTNGQGVLHY SMVLEGGNDA LKLAIDNALS ITSDGLTIRL 100
    EGGVEPNKPV RYSYTRQARG SWSLNWLVPI GHEKPSNIKV FIHELNAGNQ 150
    LSHMSPIYTI EMGDELLAKL ARDATFFVRA HESNEMQPTL AISHAGVSVV 200
    MAQAQPRREK RWSEWASGKV LCLLDPLDGV YNYLAQQRCN LDDTWEGKIY 250
    RVLAGNPAKH DLDIKPTVIS HRLHFPEGGS LAALTAHQAC HLPLETFTRH 300
    RQPRGWEQLE QCGYPVQRLV ALYLAARLSW NQVDQVIRNA LASPGSGGDL 350
    GEAIREQPEQ ARLALTLAAA ESERFVRQGT GNDEAGAASA DVVSLTCPVA 400
    AGECAGPADS GDALLERNYP TGAEFLGDGG DISFSTRGTQ NWTVERLLQA 450
    HRQLEERGYV FVGYHGTFLE AAQSIVFGGV RARSQDLDAI WRGFYIAGDP 500
    ALAYGYAQDQ EPDARGRIRN GALLRVYVPR SSLPGFYRTG LTLAAPEAAG 550
    EVERLIGHPL PLRLDAITGP EEEGGRLETI LGWPLAERTV VIPSAIPTDP 600
    RNVGGDLDPS SIPDKEQAIS ALPDYASQPG KPPREDLK 638
    Length:638
    Mass (Da):69,284
    Last modified:January 11, 2001 - v2
    Checksum:i7B9AAD56A27C700A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti4 – 41T → I in AAB59097. (PubMed:6201861)Curated
    Sequence conflicti22 – 221F → S in AAB59097. (PubMed:6201861)Curated
    Sequence conflicti204 – 2041A → T in AAB59097. (PubMed:6201861)Curated
    Sequence conflicti389 – 3891S → N in AAB59097. (PubMed:6201861)Curated
    Sequence conflicti432 – 4321I → V in AAB59097. (PubMed:6201861)Curated
    Sequence conflicti540 – 5401G → S in AAB59097. (PubMed:6201861)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01397 Genomic DNA. Translation: AAB59097.1.
    AE004091 Genomic DNA. Translation: AAG04537.1.
    PIRiA30347.
    C83503.
    RefSeqiNP_249839.1. NC_002516.2.

    Genome annotation databases

    EnsemblBacteriaiAAG04537; AAG04537; PA1148.
    GeneIDi877850.
    KEGGipae:PA1148.
    PATRICi19836616. VBIPseAer58763_1194.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01397 Genomic DNA. Translation: AAB59097.1 .
    AE004091 Genomic DNA. Translation: AAG04537.1 .
    PIRi A30347.
    C83503.
    RefSeqi NP_249839.1. NC_002516.2.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AER X-ray 2.30 A/B 425-634 [» ]
    1DMA X-ray 2.50 A/B 425-638 [» ]
    1IKP X-ray 1.45 A 26-638 [» ]
    1IKQ X-ray 1.62 A 26-638 [» ]
    1XK9 X-ray 2.10 A/B 424-638 [» ]
    1ZM2 X-ray 3.07 B/D/F 424-630 [» ]
    1ZM3 X-ray 3.07 B/D/F 424-630 [» ]
    1ZM4 X-ray 2.90 B/D/F 424-630 [» ]
    1ZM9 X-ray 2.80 B/D/F 424-630 [» ]
    2ZIT X-ray 3.00 B/D/F 425-630 [» ]
    3B78 X-ray 2.50 B/D/F 425-630 [» ]
    3B82 X-ray 2.35 B/D/F 425-630 [» ]
    3B8H X-ray 2.50 B/D/F 425-630 [» ]
    ProteinModelPortali P11439.
    SMRi P11439. Positions 27-631.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 208964.PA1148.

    Chemistry

    DrugBanki DB00131. Adenosine monophosphate.

    Protein family/group databases

    TCDBi 1.C.73.1.1. the pseudomonas exotoxin a (p-exoa) family.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblBacteriai AAG04537 ; AAG04537 ; PA1148 .
    GeneIDi 877850.
    KEGGi pae:PA1148.
    PATRICi 19836616. VBIPseAer58763_1194.

    Organism-specific databases

    PseudoCAPi PA1148.

    Phylogenomic databases

    HOGENOMi HOG000081585.
    KOi K11020.
    OMAi AHESNEM.
    OrthoDBi EOG6ZPSVM.

    Enzyme and pathway databases

    BioCyci MetaCyc:MONOMER-15587.
    SABIO-RK P11439.

    Miscellaneous databases

    EvolutionaryTracei P11439.

    Family and domain databases

    Gene3Di 2.60.120.200. 1 hit.
    3.90.1350.10. 1 hit.
    InterProi IPR008985. ConA-like_lec_gl_sf.
    IPR013320. ConA-like_subgrp.
    IPR015185. Exotox-A_bind.
    IPR015099. Exotox-A_cataly_dom.
    IPR015186. Exotox-A_middle_dom.
    [Graphical view ]
    Pfami PF09101. Exotox-A_bind. 1 hit.
    PF09009. Exotox-A_cataly. 1 hit.
    PF09102. Exotox-A_target. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49899. SSF49899. 1 hit.
    SSF56864. SSF56864. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Cloning, nucleotide sequence, and expression in Escherichia coli of the exotoxin A structural gene of Pseudomonas aeruginosa."
      Gray G.L., Smith D.H., Baldridge J.S., Harkins R.N., Vasil M.L., Chen E.Y., Heyneker H.L.
      Proc. Natl. Acad. Sci. U.S.A. 81:2645-2649(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 26-53.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.
    3. "Active site of Pseudomonas aeruginosa exotoxin A. Glutamic acid 553 is photolabeled by NAD and shows functional homology with glutamic acid 148 of diphtheria toxin."
      Carroll S.F., Collier R.J.
      J. Biol. Chem. 262:8707-8711(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVE SITE.
    4. "Mutagenesis of Pseudomonas exotoxin in identification of sequences responsible for the animal toxicity."
      Chaudhary V.K., Jinno Y., Galo M.G., Fitzgerald D., Pastan I.
      J. Biol. Chem. 265:16306-16310(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAINS.
    5. "Biochemical and immunochemical studies of proteolytic fragments of exotoxin A from Pseudomonas aeruginosa."
      Bourdenet S., Vacheron M.-J., Guinand M., Michel G., Arminjon F.
      Eur. J. Biochem. 192:379-385(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAINS.
    6. "The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A."
      Kounnas M.Z., Morris R.E., Thompson M.R., FitzGerald D.J., Strickland D.K., Saelinger C.B.
      J. Biol. Chem. 267:12420-12423(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: RECEPTOR-BINDING, MUTAGENESIS OF LYS-82.
    7. "Reduction of furin-nicked Pseudomonas exotoxin A: an unfolding story."
      McKee M.L., FitzGerald D.J.
      Biochemistry 38:16507-16513(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISULFIDE BOND.
    8. Cited for: FUNCTION AS A TOXIN, FUNCTION AS A GLYCOHYDROLASE, FUNCTION AS AN ADP-RIBOSYLTRANSFERASE, MUTAGENESIS OF GLU-578.
    9. "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: ENZYME REGULATION, LETHAL DOSE.
    10. "The crystal structure of Pseudomonas aeruginosa exotoxin domain III with nicotinamide and AMP: conformational differences with the intact exotoxin."
      Li M., Dyda F., Benhar I., Pastan I., Davies D.R.
      Proc. Natl. Acad. Sci. U.S.A. 92:9308-9312(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 424-638.
    11. "Crystal structure of the catalytic domain of Pseudomonas exotoxin A complexed with a nicotinamide adenine dinucleotide analog: implications for the activation process and for ADP ribosylation."
      Li M., Dyda F., Benhar I., Pastan I., Davies D.R.
      Proc. Natl. Acad. Sci. U.S.A. 93:6902-6906(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 424-638.
    12. "The nature and character of the transition state for the ADP-ribosyltransferase reaction."
      Jorgensen R., Wang Y., Visschedyk D., Merrill A.R.
      EMBO Rep. 9:802-809(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 425-630 IN COMPLEX WITH YEAST EEF2 AND NAD, MUTAGENESIS OF ARG-481; GLU-571; ARG-576 AND GLU-578.

    Entry informationi

    Entry nameiTOXA_PSEAE
    AccessioniPrimary (citable) accession number: P11439
    Secondary accession number(s): Q9I4I7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: January 11, 2001
    Last modified: October 1, 2014
    This is version 122 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

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

    External Data

    Dasty 3