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Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the anaphase-promoting complex/cyclosome (APC/C), a 13-subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic [...]

A study was conducted to determine the effect of thapsigargin (TG) inhibitor on [Ca.sup.2}-free crystals of sarcoplasmic reticulum [Ca.sup.2}-ATPase. The findings reveal the flexibility of the loops connecting the transmembrane and cytosolic domains in the ATPase.

Telomere shortening has been implicated in the aging process and various age-associated disorders, including renal disease. Moreover, oxidative stress has been identified as an initiator of accelerated telomere shortening. We have shown previously that maternal protein restriction during lactation leads to reduced renal telomere shortening, reduced albuminuria, and increased longevity in rats. Here we address the hypothesis that maternal protein restriction during lactation is nephroprotective and associated with increased expression of antioxidative enzymes and decreased age-dependent renal telomere shortening. Newborn rats were suckled by a dam fed either a control (20% protein) or low-protein (8% protein) diet. All animals were weaned onto standard chow. Offspring that had been suckled by proteinrestricted mothers had reduced albuminuria, N-acetyl-glucosaminidase, and urinary aldosterone excretion. These animals also did not show significant age-dependent renal telomere shortening and hence had significantly longer telomeres at 12 mo of age. This lack of renal telomere shortening was associated with increased levels of the antioxidant enzymes manganese superoxide dismutase, glutathione peroxidase, and glutathione reductase. These findings suggest that beneficial effects of slow growth during lactation are associated with increased antioxidant capacity and prevention of age-dependent telomere shortening in the kidney. renal disease; albuminuria; telomeres; antioxidant enzymes

Genetic evidence suggests that inhibition of amyloid fibril formation by small molecules should be effective against amyloid diseases. Known amyloid inhibitors appear to function by shifting the aggregation equilibrium away from the amyloid state. Here, we describe a series of transthyretin amyloidosis inhibitors that functioned by increasing the kinetic barrier associated with misfolding, preventing amyloidogenesis by stabilizing the native state. The trans-suppressor mutation, threonine 119 → methionine 119, which is known to ameliorate familial amyloid disease, also functioned through kinetic stabilization, implying that this small-molecule strategy should be effective in treating amyloid diseases., Hundreds of human diseases, including the amyloidoses, are associated with protein misfolding (1-5). The 80 familial mutations that exacerbate [for example, [Val.sup.30] → [Met.sup.30] (V30M) and [Leu.sup.55] → [Pro.sup.55] (L55P) [...]

Acid-base chemistry of nicotine is discussed as a nice example of equilibria in aqueous solution where the major form in which the solute is actually present depends on the pH of the solution. Topics include the fractional concentration of N (neutral), of N(super.1+) (the monocation), of N(super.2+) (the dication), the other conjugate acid of nicotine, and applications to amino acids and to enzyme kinetics.

Research has been conducted on the pathogenic bacterium Klebsiella aerogenes. The catalysis of urea hydrolysis by means of a the bacterium' dinuclear nickel site is described.

Research has been conducted on the peptide deformylase. The removal of the N-terminal formyl group from synthesized polypeptides has been carried out.

Research has been conducted on the cyanyl radical. The investigation of the cyanyl radical inhibition mechanism has been carried out.

Research has been conducted on the protein inhibitor eglin c. The synthesis of the wild-type eglin c has been carried out.

Research has been conducted on the spinach cytochrome complex. The inhibition of the complex by Cu (super)2+ in the presence of 1.6 (mu)M decyl-plastoquinol as a substrate is examined.

Research has been conducted on the glutamate semialdehyde aminomutase. The reactions of the enzyme with diaminopropyl sulfate R- and S-enantiomers have been investigated.

Research has been conducted on the transition-state analogue 2-phosphoglycolate (2PG) bound to methylglyoxal synthase. The crystal structure of 2PG has been investigated.

Research has been conducted on the kinesin motor proteins. The identification of small organic ligands in inhibiting kinesin's activity has been carried out.