tailieunhanh - Báo cáo khoa học: A family of killer toxins Exploring the mechanism of ADP-ribosylating toxins

The ADP-ribosylating toxins (ADPRTs) are a family of toxins that cata-lyse the hydrolysis of NAD and the transfer of the ADP-ribose moiety onto a target. This family includes many notorious killers, responsible for thousands of deaths annually including: cholera, enterotoxic Escheri-chia coli, whooping cough, diphtheria and a plethora of Clostridialbinary toxins. | IFEBS Journal REVIEW ARTICLE A family of killer toxins Exploring the mechanism of ADP-ribosylating toxins Kenneth P. Holbourn1 Clifford C. Shone2 and K. R. Acharya1 1 Department of Biology and Biochemistry University of Bath UK 2 Health Protection Agency Porton Down Salisbury UK Keywords ADP-ribosylating toxin ADP-ribosyltransferase GTPases NAD binding structure Correspondence K. R. Acharya Department of Biology and Biochemistry Building 4 South University of Bath Claverton Down Bath BA2 7AY UK Fax 44 1225 386779 Tel 44 1225 386238 E-mail Received 12 June 2006 revised 27 July 2006 accepted 31 July 2006 doi The ADP-ribosylating toxins ADPRTs are a family of toxins that catalyse the hydrolysis of NAD and the transfer of the ADP-ribose moiety onto a target. This family includes many notorious killers responsible for thousands of deaths annually including cholera enterotoxic Escherichia coli whooping cough diphtheria and a plethora of Clostridial binary toxins. Despite their notoriety as pathogens the ADPRTs have been extensively used as cellular tools to study and elucidate the functions of the small GTPases that they target. There are four classes of ADPRTs and at least one structure representative of each of these classes has been determined. They all share a common fold and several motifs around the active site that collectively facilitate the binding and transfer of the ADP-ribose moiety of NAD to their protein targets. In this review we present an overview of the physiology and cellular qualities of the bacterial ADPRTs and take an in-depth look at the structural motifs that differentiate the different classes of bacterial ADPRTs in relation to their function. Pathogenic bacteria are known to possess an arsenal of toxins and effectors that assist them in targeting and killing their host cells. The ADP-ribosylating toxins ADPRTs are a large family of dangerous and potentially lethal toxins. Examples of these