Oxidation of methionine residues in calmodulin (CaM) lowers the affinity for calcium and results in an inability to activate target proteins fully. To evaluate the structural consequences of CaM oxidation, we used infrared difference spectroscopy to identify oxidation-dependent effects on protein conformation and calcium liganding. Oxidation-induced changes include an increase in hydration of a...

Almost unequivocally, aging and neurodegeneration lead to deficits in neural information processing. These declines are marked by increased neural noise that is associated with increased variability or inconsistency in behavioral patterns. While it is often viewed that these problems arise from dysregulation of dopamine (DA), a monoamine modulator, glutamate (GLU), an excitatory amino acid that...

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Proteasomes are the primary sites for protein degradation in mammalian cells. Each proteasome particle contains two chymotrypsin-like, two trypsin-like, and two caspase-like proteolytic sites. Previous studies suggest a complex network of allosteric interactions between these catalytic and multiple regulatory sites. We used positional scanning combinatorial substrate libraries to determine the ...

Degenerative disc disease has been implicated as a major component of spine pathology. However, although biological repair of the degenerate disk would be the ideal treatment, there is no universally accepted scaffold for tissue engineering of the intervertebral disk. To help remedy this, we investigated the gelation kinetics of various concentrations (2.5 to 10%) of two water-soluble chitosan ...

Kinesin is a microtubule-dependent motor protein. We have recently determined the X-ray structure of monomeric and dimeric kinesin from rat brain. The dimer consists of two motor domains, held together by their alpha-helical neck domains forming a coiled coil. Here we analyze the nature of the interactions in the neck domain (residues 339-370). Overall, the neck helix shows a heptad repeat (abc...

EmrE is a small H+-coupled multidrug transporter in Escherichia coli. Claims have been made for an antiparallel topology of this homodimeric protein. However, our own biochemical studies performed with detergent-solubilized purified protein support a parallel topology of the protomers. We developed an alternative approach to constrain the relative topology of the protomers within the dimer so t...

Sirotnak, F. M. (Sloan-Kettering Institute for Cancer Research, New York, N.Y.), Gloria J. Donati, and Dorris J. Hutchison. Folic acid derivatives synthesized during growth of Diplococcus pneumoniae. J. Bacteriol. 85:658-665. 1963.-Under cultural conditions permitting synthesis of folic acid in an amount greatly in excess (20- to 30-fold) of that required for maximal growth of Diplococcus pneum...