Exercise prescription principles for persons without chronic disease and/or disability are based on well developed scientific information. While there are varied objectives for being physically active, including enhancing physical fitness, promoting health by reducing the risk for chronic disease and ensuring safety during exercise participation, the essence of the exercise prescription is based on individual interests, health needs and clinical status, and therefore the aforementioned goals do not always carry equal weight. In the same manner, the principles of exercise prescription for persons with chronic disease and/or disability should place more emphasis on the patient's clinical status and, as a result, the exercise mode, intensity, frequency and duration are usually modified according to their clinical condition. Presently, these exercise prescription principles have been scientifically defined for clients with coronary heart disease. However, other diseases and/or disabilities have been studied less (e.g. renal failure, cancer, chronic fatigue syndrome, cerebral palsy). This article reviews these issues with specific reference to persons with chronic diseases and disabilities.

Cellvibrio japonicus arabinanase Arb43A hydrolyzes the alpha-1,5-linked L-arabinofuranoside backbone of plant cell wall arabinans. The three-dimensional structure of Arb43A, determined at 1.9 A resolution, reveals a five-bladed beta-propeller fold. Arb43A is the first enzyme known to display this topology. A long V-shaped surface groove, partially enclosed at one end, forms a single extended substrate-binding surface across the face of the propeller. Three carboxylates deep in the active site groove provide the general acid and base components for glycosidic bond hydrolysis with inversion of anomeric configuration.

Glycosylation of macrolide antibiotics confers host cell immunity from endogenous and exogenous agents. The Streptomyces antibioticus glycosyltransferases, OleI and OleD, glycosylate and inactivate oleandomycin and diverse macrolides including erythromycin, respectively. The structure of these enzyme–ligand complexes, in tandem with kinetic analysis of site-directed variants, provide insight into the interaction of macrolides with their synthetic apparatus. Erythromycin binds to OleD and the 23S RNA of its target ribosome in the same conformation and, although the antibiotic contains a large number of polar groups, its interaction with these macromolecules is primarily through hydrophobic contacts. Erythromycin and oleandomycin, when bound to OleD and OleI, respectively, adopt different conformations, reflecting a subtle effect on sugar positioning by virtue of a single change in the macrolide backbone. The data reported here provide structural insight into the mechanism of resistance to both endogenous and exogenous antibiotics, and will provide a platform for the future redesign of these catalysts for antibiotic remodelling.

1 FPL 67156 (6-N,N-diethyl-p,'y-dibromomethylene-D-ATP), is a newly synthesized analogue of ATP. 2 In a rabbit isolated tracheal epithelium preparation, measuring P2U-purinoceptor-dependent

Solvent organization is a key but underexploited contributor to the thermodynamics of protein−ligand recognition, with implications for ligand discovery, drug resistance, and protein engineering. Here, we explore the contribution of solvent to ligand binding in the Haemophilus influenzae virulence protein SiaP. By introducing a single mutation without direct ligand contacts, we observed a >1000-fold change in sialic acid binding affinity. Crystallographic and calorimetric data of wild-type and mutant SiaP showed that this change results from an enthalpically unfavorable perturbation of the solvent network. This disruption is reflected by changes in the normalized atomic displacement parameters of crystallographic water molecules. In SiaP's enclosed cavity, relative differences in water-network dynamics serve as a simple predictor of changes in the free energy of binding upon changing protein, ligand, or both. This suggests that solvent structure is an evolutionary constraint on protein sequence that contributes to ligand affinity and selectivity.