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P11439

- TOXA_PSEAE

UniProt

P11439 - TOXA_PSEAE

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Protein
Exotoxin A
Gene
eta, PA1148
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

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 – 4741NAD
Active sitei578 – 57811 Publication
Binding sitei578 – 5781NAD

Regions

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

GO - Molecular functioni

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

GO - Biological processi

  1. metabolic process Source: GOC
Complete GO annotation...

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 Publication
Add
BLAST
Chaini26 – 638613Exotoxin A
PRO_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

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.

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 – 42940IB
Add
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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti4 – 41T → I in AAB59097. 1 Publication
Sequence conflicti22 – 221F → S in AAB59097. 1 Publication
Sequence conflicti204 – 2041A → T in AAB59097. 1 Publication
Sequence conflicti389 – 3891S → N in AAB59097. 1 Publication
Sequence conflicti432 – 4321I → V in AAB59097. 1 Publication
Sequence conflicti540 – 5401G → S in AAB59097. 1 Publication

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

« Hide 'large scale' publications
  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: June 11, 2014
This is version 121 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

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