1dma | pdb_00001dma
DOMAIN III OF PSEUDOMONAS AERUGINOSA EXOTOXIN COMPLEXED WITH NICOTINAMIDE AND AMP
Structural highlights
Function[TOXA_PSEAE] 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 LD(50) of 65 ng/ml against the human lung epithelial cell line C38.[1] Publication Abstract from PubMedDomain III of Pseudomonas aeruginosa exotoxin A catalyses the transfer of ADP-ribose from NAD to a modified histidine residue of elongation factor 2 in eukaryotic cells, thus inactivating elongation factor 2. This domain III is inactive in the intact toxin but is active in the isolated form. We report here the 2.5-A crystal structure of this isolated domain crystallized in the presence of NAD and compare it with the corresponding structure in the intact Pseudomonas aeruginosa exotoxin A. We observe a significant conformational difference in the active site region from Arg-458 to Asp-463. Contacts with part of domain II in the intact toxin prevent the adoption of the isolated domain conformation and provide a structural explanation for the observed inactivity. Additional electron density in the active site region corresponds to separate AMP and nicotinamide and indicates that the NAD has been hydrolyzed. The structure has been compared with the catalytic domain of the diphtheria toxin, which was crystallized with ApUp. 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 DR Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9308-12. PMID:7568123[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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