1aer

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spinqualitylabelsall models 1aer, resolution 2.3Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

DOMAIN III OF PSEUDOMONAS AERUGINOSA EXOTOXIN COMPLEXED WITH BETA-TAD

Overview

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.

About this Structure

1AER is a Single protein structure of sequence from Pseudomonas aeruginosa with TIA, TAD and AMP as ligands. Full crystallographic information is available from OCA.

Reference

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 DR, Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6902-6. PMID:8692916

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