1AER

DOMAIN III OF PSEUDOMONAS AERUGINOSA EXOTOXIN COMPLEXED WITH BETA-TAD

Summary for 1AER

• Entry DOI: 10.2210/pdb1aer/pdb
• Descriptor: EXOTOXIN A, BETA-METHYLENE-THIAZOLE-4-CARBOXYAMIDE-ADENINE DINUCLEOTIDE, 2-(1,5-DIDEOXYRIBOSE)-4-AMIDO-THIAZOLE, ... (5 entities in total)
• Functional Keywords: toxin, adp-ribosylation, transferase, glycosyltransferase, nad
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 47096.13

Authors

Li, M.,Dyda, F.,Benhar, I.,Pastan, I.,Davies, D.R. (deposition date: 1995-12-11, release date: 1996-06-10, Last modification date: 2024-06-05)

Primary citation

Li, M.,Dyda, F.,Benhar, I.,Pastan, I.,Davies, D.R.
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.USA, 93:6902-6906, 1996

PubMed Abstract: The catalytic, or third domain of Pseudomonas exotoxin A (PEIII) catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, inhibiting protein synthesis. We have determined the structure of PEIII crystallized in the presence of NAD to define the site of binding and mechanism of activation. However, NAD undergoes a slow hydrolysis and the crystal structure revealed only the hydrolysis products, AMP and nicotinamide, bound to the enzyme. To better define the site of NAD binding, we have now crystallized PEIII in the presence of a less hydrolyzable NAD analog, beta-methylene-thiazole-4-carboxamide adenine dinucleotide (beta-TAD), and refined the complex structure at 2.3 angstroms resolution. There are two independent molecules of PEIII in the crystal, and the conformations of beta-TAD show some differences in the two binding sites. The beta-TAD attached to molecule 2 appears to have been hydrolyzed between the pyrophosphate and the nicotinamide ribose. However molecule 1 binds to an intact beta-TAD and has no crystal packing contacts in the vicinity of the binding site, so that the observed conformation and interaction with the PEIII most likely resembles that of NAD bound to PEIII in solution. We have compared this complex with the catalytic domains of diphtheria toxin, heat labile enterotoxin, and pertussis toxin, all three of which it closely resembles.

PubMed: 8692916
DOI: 10.1073/pnas.93.14.6902

Experimental method

X-RAY DIFFRACTION (2.3 Å)