Exotoxin A

NameExotoxin A
Synonyms
  • 2.4.2.36
  • ETA
  • NAD(+)--diphthamide ADP-ribosyltransferase
  • PE
Gene Nameeta
OrganismPseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Amino acid sequence
>lcl|BSEQ0011340|Exotoxin A
MHLTPHWIPLVASLGLLAGGSFASAAEEAFDLWNECAKACVLDLKDGVRSSRMSVDPAIA
DTNGQGVLHYSMVLEGGNDALKLAIDNALSITSDGLTIRLEGGVEPNKPVRYSYTRQARG
SWSLNWLVPIGHEKPSNIKVFIHELNAGNQLSHMSPIYTIEMGDELLAKLARDATFFVRA
HESNEMQPTLAISHAGVSVVMAQAQPRREKRWSEWASGKVLCLLDPLDGVYNYLAQQRCN
LDDTWEGKIYRVLAGNPAKHDLDIKPTVISHRLHFPEGGSLAALTAHQACHLPLETFTRH
RQPRGWEQLEQCGYPVQRLVALYLAARLSWNQVDQVIRNALASPGSGGDLGEAIREQPEQ
ARLALTLAAAESERFVRQGTGNDEAGAASADVVSLTCPVAAGECAGPADSGDALLERNYP
TGAEFLGDGGDISFSTRGTQNWTVERLLQAHRQLEERGYVFVGYHGTFLEAAQSIVFGGV
RARSQDLDAIWRGFYIAGDPALAYGYAQDQEPDARGRIRNGALLRVYVPRSSLPGFYRTG
LTLAAPEAAGEVERLIGHPLPLRLDAITGPEEEGGRLETILGWPLAERTVVIPSAIPTDP
RNVGGDLDPSSIPDKEQAISALPDYASQPGKPPREDLK
Number of residuesNone
Molecular Weight69283.345
Theoretical pI5.29
GO Classification
Functions
  • NAD+-diphthamide ADP-ribosyltransferase activity
Processes
Components
General FunctionNad+-diphthamide adp-ribosyltransferase activity
Specific FunctionAn 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 LD(50) of 65 ng/ml against the human lung epithelial cell line C38.
Transmembrane Regions
GenBank Protein ID
UniProtKB IDP11439
UniProtKB Entry Name
Cellular LocationNone
Gene sequence
>lcl|BSEQ0011341|Exotoxin A (eta)
ATGCACCTGACACCCCATTGGATCCCCCTGGTCGCCAGCCTCGGCCTGCTCGCCGGCGGC
TCGTTCGCGTCCGCCGCCGAGGAAGCCTTCGACCTCTGGAACGAATGCGCCAAGGCCTGC
GTGCTCGACCTCAAGGACGGCGTGCGTTCCAGCCGCATGAGCGTCGACCCGGCCATCGCC
GACACCAACGGCCAGGGCGTGCTGCACTACTCCATGGTCCTGGAGGGCGGCAACGACGCG
CTCAAGCTGGCCATCGACAACGCCCTCAGCATCACCAGCGACGGCCTGACCATCCGCCTC
GAAGGTGGCGTCGAGCCGAACAAGCCGGTGCGCTACAGCTACACGCGCCAGGCGCGCGGC
AGTTGGTCGCTGAACTGGCTGGTGCCGATCGGCCACGAGAAGCCTTCGAACATCAAGGTG
TTCATCCACGAACTGAACGCCGGTAACCAGCTCAGCCACATGTCGCCGATCTACACCATC
GAGATGGGCGACGAGTTGCTGGCGAAGCTGGCGCGCGATGCCACCTTCTTCGTCAGGGCG
CACGAGAGCAACGAGATGCAGCCGACGCTCGCCATCAGCCATGCCGGGGTCAGCGTGGTC
ATGGCCCAGGCCCAGCCGCGCCGGGAAAAGCGCTGGAGCGAATGGGCCAGCGGCAAGGTG
TTGTGCCTGCTCGACCCGCTGGACGGGGTCTACAACTACCTCGCCCAGCAGCGCTGCAAC
CTCGACGATACCTGGGAAGGCAAGATCTACCGGGTGCTCGCCGGCAACCCGGCGAAGCAT
GACCTGGACATCAAGCCCACGGTCATCAGTCATCGCCTGCATTTCCCCGAGGGCGGCAGC
CTGGCCGCGCTGACCGCGCACCAGGCCTGCCACCTGCCGCTGGAGACCTTCACCCGTCAT
CGCCAGCCGCGCGGCTGGGAACAACTGGAGCAGTGCGGCTATCCGGTGCAGCGGCTGGTC
GCCCTCTACCTGGCGGCGCGGCTGTCGTGGAACCAGGTCGACCAGGTGATCCGCAACGCC
CTGGCCAGCCCCGGCAGCGGCGGCGACCTGGGCGAAGCGATCCGCGAGCAGCCGGAGCAG
GCCCGTCTGGCCCTGACCCTGGCCGCCGCCGAGAGCGAGCGCTTCGTCCGGCAGGGCACA
GGCAACGACGAGGCCGGCGCGGCCAGCGCCGACGTGGTGAGCCTGACCTGCCCGGTCGCC
GCCGGTGAATGCGCGGGCCCGGCGGACAGCGGCGACGCCCTGCTGGAGCGCAACTATCCC
ACTGGCGCGGAGTTCCTCGGCGACGGCGGCGACATCAGCTTCAGCACCCGCGGCACGCAG
AACTGGACGGTGGAGCGGCTGCTCCAGGCGCACCGCCAACTGGAGGAGCGCGGCTATGTG
TTCGTCGGCTACCACGGCACCTTCCTCGAAGCGGCGCAAAGCATCGTCTTCGGCGGGGTG
CGCGCGCGCAGCCAGGACCTCGACGCGATCTGGCGCGGTTTCTATATCGCCGGCGATCCG
GCGCTGGCCTACGGCTACGCCCAGGACCAGGAACCCGACGCGCGCGGCCGGATCCGCAAC
GGTGCCCTGCTGCGGGTCTATGTGCCGCGCTCGAGTCTGCCGGGCTTCTACCGCACCGGC
CTGACCCTGGCCGCGCCGGAGGCGGCGGGCGAGGTCGAACGGCTGATCGGCCATCCGCTG
CCGCTGCGCCTGGACGCCATCACCGGCCCCGAGGAGGAAGGCGGGCGCCTGGAGACCATT
CTCGGCTGGCCGCTGGCCGAGCGCACCGTGGTGATTCCCTCGGCGATCCCCACCGACCCG
CGCAACGTCGGCGGCGACCTCGACCCGTCCAGCATCCCCGACAAGGAACAGGCGATCAGC
GCCCTGCCGGACTACGCCAGCCAGCCCGGCAAACCGCCGCGCGAGGACCTGAAGTAA
GenBank Gene ID
GeneCard IDNone
GenAtlas ID
HGNC ID
Chromosome LocationNone
LocusNone
References
  1. Gray GL, Smith DH, Baldridge JS, Harkins RN, Vasil ML, Chen EY, Heyneker HL: Cloning, nucleotide sequence, and expression in Escherichia coli of the exotoxin A structural gene of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 1984 May;81(9):2645-9. [6201861 ]
  2. Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV: Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature. 2000 Aug 31;406(6799):959-64. [10984043 ]
  3. Carroll SF, Collier RJ: 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. J Biol Chem. 1987 Jun 25;262(18):8707-11. [2885323 ]
  4. Chaudhary VK, Jinno Y, Gallo MG, FitzGerald D, Pastan I: Mutagenesis of Pseudomonas exotoxin in identification of sequences responsible for the animal toxicity. J Biol Chem. 1990 Sep 25;265(27):16306-10. [2118903 ]
  5. Bourdenet S, Vacheron MJ, Guinand M, Michel G, Arminjon F: Biochemical and immunochemical studies of proteolytic fragments of exotoxin A from Pseudomonas aeruginosa. Eur J Biochem. 1990 Sep 11;192(2):379-85. [2170123 ]
  6. Kounnas MZ, Morris RE, Thompson MR, FitzGerald DJ, Strickland DK, Saelinger CB: The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds and internalizes Pseudomonas exotoxin A. J Biol Chem. 1992 Jun 25;267(18):12420-3. [1618748 ]
  7. McKee ML, FitzGerald DJ: Reduction of furin-nicked Pseudomonas exotoxin A: an unfolding story. Biochemistry. 1999 Dec 14;38(50):16507-13. [10600112 ]
  8. Jorgensen R, Purdy AE, Fieldhouse RJ, Kimber MS, Bartlett DH, Merrill AR: Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae. J Biol Chem. 2008 Apr 18;283(16):10671-8. doi: 10.1074/jbc.M710008200. Epub 2008 Feb 14. [18276581 ]
  9. Turgeon Z, Jorgensen R, Visschedyk D, Edwards PR, Legree S, McGregor C, Fieldhouse RJ, Mangroo D, Schapira M, Merrill AR: Newly discovered and characterized antivirulence compounds inhibit bacterial mono-ADP-ribosyltransferase toxins. Antimicrob Agents Chemother. 2011 Mar;55(3):983-91. doi: 10.1128/AAC.01164-10. Epub 2010 Dec 6. [21135177 ]
  10. Li M, Dyda F, Benhar I, Pastan I, Davies DR: The crystal structure of Pseudomonas aeruginosa exotoxin domain III with nicotinamide and AMP: conformational differences with the intact exotoxin. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9308-12. [7568123 ]
  11. Li M, Dyda F, Benhar I, Pastan I, Davies DR: 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. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6902-6. [8692916 ]
  12. Jorgensen R, Wang Y, Visschedyk D, Merrill AR: The nature and character of the transition state for the ADP-ribosyltransferase reaction. EMBO Rep. 2008 Aug;9(8):802-9. doi: 10.1038/embor.2008.90. Epub 2008 Jun 27. [18583986 ]

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