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Twenty percent of the familial form of amyotrophic lateral sclerosis (ALS) is caused by mutations in the Cu, Zn-superoxide dismutase gene (SOD1) through the gain of a toxic function. The nature of this toxic function of mutant SOD1 has remained largely unknown. Here we show that WT SOD1 not only hastens onset of the ALS phenotype but can also convert an(More)
A triple mutant of murine epidermal growth factor (mEGF), N1Q/H22Y/R45K-mEGF, was constructed by site-directed mutagenesis, expressed, purified, and characterized for use in an affinity cross-linking study to identify aminoacyl residues of the EGF receptor adjacent to a residue in the carboxyl-terminal domain of bound EGF thought to be important in(More)
The enhancement of calmodulin's (CaM) calcium binding activity by an enzyme or a recognition site peptide and its diminution by key point mutations at the protein recognition interface (e.g., E84K-CaM), which is more than 20 A away from the nearest calcium ligation structure, can be described by an expanded version of the Adair-Klotz equation for(More)
An apparent paradox in smooth muscle biology is the ability of unphosphorylated myosin to maintain a filamentous structure in the presence of ATP in vivo, whereas unphosphorylated myosin filaments are depolymerized in vitro in the presence of ATP. This suggests that additional uncharacterized factors are required for the stabilization of myosin filaments in(More)
The nonmuscle/smooth muscle myosin light chain kinase (MLCK) and the kinase related protein (KRP) that lacks protein kinase activity are myosin II binding proteins encoded in the vertebrate genome by a true gene within a gene relationship. The genomic organization and expression result in the same amino acid sequence in different molecular contexts from two(More)
We have determined the first genomic structure and characterized the mRNA and protein products of a novel vertebrate gene that encodes a calcium-binding protein with amino acid sequence identity to a protein kinase domain. The elucidation of the complete DNA sequence of this transcription unit and adjacent genomic DNA, Southern blot and polymerase chain(More)
Myosin light chain kinase (MLCK) is the key regulator of cell motility and smooth muscle contraction in higher vertebrates. We searched for the features of the high molecular weight MLCK (MLCK-210) associated with its unique N-terminal sequence not found in a more ubiquitous lower molecular weight MLCK (MLCK-108). MLCK-210 demonstrates stronger association(More)
Glaucoma, the second most prevalent cause of blindness worldwide, is a degenerative disease characterized by loss of vision due to loss of retinal ganglion cells. There is no cure for glaucoma, but early intervention with drugs and/or surgery may slow or halt loss of vision. Increased intraocular pressure (IOP), age, and genetic background are the leading(More)
Riluzole is the only FDA approved drug for the treatment of amyotrophic lateral sclerosis. Riluzole is assumed to be mainly metabolized by the liver cytochrome CYP1A2 and by the extra-hepatic cytochrome CYP1A1. CYP1A2 and CYP1A1 genetic polymorphisms are known, but their relationship to riluzole metabolism in ALS patients has not been investigated. The aim(More)
The apical and principal segments of the bovine acrosome contain a stable matrix complex that is bound to the outer acrosomal membrane and exhibits hydrolase-binding activity. The present study was undertaken to determine whether the outer acrosomal membrane-associated matrix complex (OMC) is composed of a unique set of acrosomal proteins and to define its(More)