Symptomatic type II protein C deficiency caused by a missense mutation (Gly 381--Ser) in the substrate-binding pocket
| Autor: | Giovanna Marchetti, A. I. Wacey, David Neil Cooper, P. Patracchini, Francesco Bernardi, Giancarlo Castaman, Egd Tuddenham, Donato Gemmati, Francesco Rodeghiero |
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| Rok vydání: | 1993 |
| Předmět: |
Adult
Models Molecular medicine.medical_specialty Reduced protein C activity Molecular Sequence Data Pregnancy Complications Cardiovascular medicine.disease_cause Polymerase Chain Reaction NO Serine Protein C deficiency Pregnancy Internal medicine Medicine Missense mutation Humans Computer Simulation Mutation Chymotrypsin biology Transition (genetics) Base Sequence Models Genetic business.industry Chromosome Mapping Protein C Deficiency Thrombosis Hematology Femoral Vein medicine.disease Molecular biology Endocrinology biology.protein Female business Protein C medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0007-1048 |
| Popis: | A patient with recurrent deep vein thrombosis and heterozygous type II deficiency, characterized by reduced protein C activity in both amidolytic and clotting functional assays, was investigated by direct sequencing of PCR fragments derived from the coding portion of the protein C gene. A G (8856) to A transition was noted in the patient which was not present in healthy controls. This mutation is predicted to cause the substitution of Ser for Gly 381, an evolutionarily conserved residue in the substrate binding pocket of serine-proteases (Gly 216, chymotrypsin numbering). A computer model of the structure of the serine-protease domain indicates that the properties of the altered protein C molecule can be explained on the basis of steric hindrance between the substituted serine and the substrate arginine side chains. |
| Databáze: | OpenAIRE |
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