RESUMEN
Nucleotide substitution in the intron 2 of HLA-DPB1*04:02:01:01 results in a novel allele, HLA-DPB1*04:02:01:44.
Asunto(s)
Alelos , Secuencia de Bases , Cadenas beta de HLA-DP , Prueba de Histocompatibilidad , Intrones , Análisis de Secuencia de ADN , Donantes de Tejidos , Humanos , Cadenas beta de HLA-DP/genética , Análisis de Secuencia de ADN/métodos , Exones , Alineación de Secuencia , Médula Ósea , CodónRESUMEN
Sequence confirmations of 175 HLA class I and II alleles in the IPD-IMGT/HLA Database.
Asunto(s)
Alelos , Bases de Datos Genéticas , Antígenos de Histocompatibilidad Clase II , Antígenos de Histocompatibilidad Clase I , Humanos , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Análisis de Secuencia de ADN , Prueba de HistocompatibilidadRESUMEN
The effects of sulfonates on the carboxypeptidase A catalyzed hydrolysis of the ester substrate benzoylglycyl-L-phenyllactate were determined. The modifiers examined were benzenesulfonate, p-toluenesulfonate, 2-phenylethane-sulfonate, methanesulfonate, ethanesulfonate, propanesulfonate, butanesulfonate, pentanesulfonate, hexanesulfonate, heptanesulfonate, and 2,2-dimethyl-2-silapentane-5-sulfonate. Sulfonate activators of peptide hydrolysis were inhibitors of esterase activity. Of the sulfonates studied, 2,2-dimethyl-2-silapentane-5-sulfonate was the most effective inhibitor. 2-Phenylethanesulfonate, hexanesulfonate, heptanesulfonate, and 2,2-dimethyl-2-silapentane-5-sulfonate exhibited uncompetitive inhibition. The remaining sulfonates either did not inhibit or the inhibition was too weak to properly characterize.
Asunto(s)
Carboxipeptidasas/antagonistas & inhibidores , Esterasas/antagonistas & inhibidores , Ácidos Sulfónicos/farmacología , Carboxipeptidasas A , Hipuratos/metabolismo , Cinética , Lactatos/metabolismoRESUMEN
A variety of modifiers of carboxypeptidase A (CPA) have been investigated in an effort to understand the structural requirements of inhibitors and activators of peptidase activity. It is proposed that an understanding of the mechanism of action of reversible activators of the enzyme may bear on the long standing question of whether the detailed mechanism of peptidase activity is different from that of esterase activity. An analog of the activator 2,2-dimethyl-2-silapentane-5-sulfonate, 5,5-dimethylhexanoate, was found to be a competitive inhibitor of the CPA-catalyzed hydrolysis of benzoylglycyl-L-phenylalanine. The modifier 4-phenyl-3-butenoate (styrylacetic acid) was determined to be an activator. The sulfonates benzene-sulfonate, p-toluenesulfonate, phenylmethanesulfonate, 2-phenylethanesulfonate, and 3-phenylpropanesulfonate were all found to be activators.
Asunto(s)
Carboxipeptidasas/metabolismo , Carboxipeptidasas A , Activación Enzimática , Hidrólisis , Cinética , Matemática , Péptidos , Inhibidores de Proteasas/farmacología , Unión Proteica , Relación Estructura-ActividadRESUMEN
The carboxypeptidase A catalyzed hydrolyses of five structurally related dipeptide substrates in the presence of the inhibitor 3-phenylpropanoate have been studied. At nonactivating substrate concentrations, 3-phenylpropanoate is a mixed inhibitor of carbobenzoxyglycyl-L-phenylalanine hydrolysis and a noncompetitive inhibitor of the hydrolyses of benzoylglycyl-L-phenylalanine, cinnamoylglycyl-L-phenylalanine, hydrocinnamoylglycyl-L-phenylalanine, and acetylglycyl-L-phenylalanine. When carbobenzoxyglycyl-L-phenylalanine and benzoylglycyl-L-phenylalanine exhibit substrate activation, inhibition by 3-phenylpropanoate is mixed but appears to be mostly competitive. Proposed here is a site for the binding of 3-phenylpropanoate along with a kinetic mechanism consistent with these data.
Asunto(s)
Carboxipeptidasas/metabolismo , Fenilpropionatos/farmacología , Activación Enzimática , Cinética , Matemática , Especificidad por SustratoRESUMEN
3,3-Diphenylpropanoate (DPP) activates the carboxypeptidase A catalyzed hydrolysis of benzoylglycyl-L-phenylalanine (BzGly-L-Phe) (Ka = 2.1 x 10 (-3) M) and inhibits ester hydrolysis uncompetitively (K1 =2.1 X 10 (-3) M). A common modifier binding site located adjacent to the peptide and ester substrate binding sites is proposed. The forms of the pathways proposed for activation and inhibition are remarkably similar.