The adhesion domain of human CD2 bears a single N-linked carbohydrate. The solution structure of a fragment of CD2 containing the covalently bound high-mannose N-glycan [-(N-acetylglucosamine)2-(mannose)5-8] was solved by nuclear magnetic resonance. The stem and two of three branches of the carbohydrate structure are well defined and the mobility of proximal glycan residues is restricted. Mutagenesis of all residues in the vicinity of the glycan suggests that the glycan is not a component of the CD2-CD58 interface; rather, the carbohydrate stabilizes the protein fold by counterbalancing an unfavorable clustering of five positive charges centered about lysine-61 of CD2.

Sleep disruption can lead to symptoms of attention-deficit hyperactivity disorder (ADHD) in children. Since periodic limb movement disorder and/or restless legs syndrome can cause sleep disruption, we assessed whether these two specific sleep disorders are likely to occur in children with ADHD. We asked a series of 69 consecutive parents of children with ADHD questions about the symptoms of periodic limb movement disorder. Based on a positive response to these periodic limb movement disorder queries, 27 children underwent all-night polysomnography. Eighteen children (aged 2 to 15 years) of the 27 (26% of the 69 children with ADHD) had 5 or more periodic leg movements in sleep per hour of sleep and had complaints of sleep disruption, thus fulfilling the criteria for periodic limb movement disorder. A comparably age- and sex-matched group of children referred to a sleep laboratory for sleep complaints but without ADHD showed only a 5% prevalence (2 of 38 subjects) of periodic leg movements in sleep (P=.017). Eight of the 18 children with ADHD and periodic limb movement disorder and one of the two control patients with periodic limb movement disorder had both a personal and parental history of restless legs syndrome symptomatology. This study further documents the occurrence of periodic limb movement disorder and restless legs syndrome in children and is the first large-scale study establishing a possible comorbidity between ADHD and periodic limb movement disorder. We propose that the sleep disruption associated with periodic limb movement disorder and restless legs syndrome and the motor restlessness of restless legs syndrome while awake could contribute to the inattention and hyperactivity seen in a subgroup of ADHD-diagnosed children.

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Molecular dynamics simulations of a single tryptophan molecule were performed using CHARMm-parametrized potential functions, where both explicit molecular and dielectric continuum models were used for the solvent. When all hydrogens were modeled explicitly, rotations about the x2 dihedral were more frequent than about the x1 dihedral. The presence of a molecular solvent damped librational motion about both dihedral angles. Conversely, when a united atom representation for hydrogen was used, rotations about the xI dihedral were more frequent than about the x2 dihedral. We show that conflicting rotamer models for the biexponential fluorescence of tryptophan zwitterion can be supported, depending on the model for hydrogen representation in the simulation. We also show that the predicted relative populations of tryptophan rotamers are not consistent with the available experimental data. Simulators are thus warned not to impute universal applicability to empirical potential energy functions found in biomacromolecular molecular mechanics packages. ( 5 ) Weiner, S. J.; Kollman, P. A.; Case, D. A,; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta, S., Jr.; Weiner, P. J. Am. Chem. Soc. 1984, 106, 765-784. (6) Weiner, S. J.; Kollman, P. A.; Nguyen, D. T.; Case, D. A.

Conformational and environmental changes in the functionally significant amino-terminal region of human parathyroid hormone (hPTH), induced by solvent or by complexation with acidic lipid, have been investigated. Structural perturbations were monitored by their effect on the fluorescence decay kinetics of the single tryptophyl residue at position 23. Data for the intact hormone were compared with those for its 1-34 and 13-34 analogues. Deletion of the 35-84 sequence had no significant effect on the structure of hPTH in the region of Trp-23, nor was there any evidence for interaction of this region with the 1-12 sequence. On the basis of a comparison of the results of this study with structural information available from other spectroscopic techniques, we propose that the local structure in the region of Trp-23 of aqueous solutions of hPTH and hPTH 1-34 has helical character. This local structure was not stable in aqueous hPTH 13-34, but was present in hPTH and its analogues, both on complexation with acidic lipid and in helix-promoting solvents. The tryptophyl fluorescence of the lipid-bound peptides was characteristic of an aqueous environment. Triple-exponential fluorescence decay kinetics were observed for the tryptophyl residue of hPTH and its deletion analogues. This can be explained in terms of ground-state heterogeneity due to the presence of three C alpha-C beta rotamers of the tryptophanyl indole side chain. Assuming this model, we show that the calculated fractional concentrations of the decay time components correlate with the likely rotamer populations and with their expected dependence on the main-chain conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

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