Active site-directed inactivation of constitutively active mutants of rhodopsin.
نویسندگان
چکیده
منابع مشابه
Active site-directed inactivation of constitutively active mutants of rhodopsin.
Recently, mutations of the active site Lys296 residue in rhodopsin (Lys296-->Glu and Lys296-->Met) have been found as the cause of disease in some patients with autosomal dominant retinitis pigmentosa. In vitro, these mutations result in constitutive activation of the protein. In an effort to develop a potential therapeutic agent for treatment of the disease, we have examined various amine deri...
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The activated (R*) states in constitutively active mutants (CAMs) of G-protein-coupled receptors (GPCRs) are presumably characterized by lower energies than the resting (R) states. If specific configurations of TM helices differing by rotations along the long transmembrane axes possess energies lower than that in the R state for pronounced CAMs, but not for non-CAMs, these particular configurat...
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Variants of dihydrofolate reductase (DHFR), which confer resistance to antifolates, are used as dominant selectable markers in vitro and in vivo and may be useful in the context of gene therapy. To identify improved mutant human DHFRs with increased catalytic efficiency and decreased binding to methotrexate, we constructed by site-directed mutagenesis four variants with substitutions at both Le...
متن کاملThe active-site environment of rhodopsin.
The 11-cis-retinal binding site of rhodopsin is of great interest because it is buried in the membrane but yet must provide an environment for charged amino acids. In addition, the active-site lysine residue must be able to engage in rapid Schiff base formation with 11-cis-retinal at neutral and lower pH values. This requires that this lysine be unprotonated. We have begun to study the environm...
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Derivatives of phenyl-keto butenoic acids have been reported to be inhibitors of pyruvate decarboxylase, (PDC). The inhibition of transketolase, a thiamine requiring enzyme such as PDF, by meta nitrophenyl derivative of 2-oxo-3-butenoic acid (MNPB) is reported here. These studies indicate that the inhibitor binds to the enzyme at the active site. A two-step inhibition was observed, first th...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 1994
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(17)37403-3