Determination of the P1′, P2′ and P3′ subsite-specificity of factor Xa
| Autor: | Robert N. Pike, Justin P. Ludeman, Bernard Le Bonniec, Julia Cianci, Peter J. Duggan, James C. Whisstock, Stephen P. Bottomley, Karen Maree Bromfield |
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| Rok vydání: | 2003 |
| Předmět: |
Stereochemistry
medicine.medical_treatment Cleavage (embryo) Biochemistry Fluorescence Substrate Specificity Peptide substrate Thrombin Peptide Library Coagulation cascade medicine Animals Serine protease chemistry.chemical_classification Protease biology Chemistry Cell Biology Kinetics DMSO - Dimethylsulphoxide Enzyme Factor Xa biology.protein Cattle Peptides medicine.drug |
| Zdroj: | Monash University |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/s1357-2725(02)00128-0 |
| Popis: | Factor Xa is a central protease in the coagulation cascade and the target for many anticoagulant compounds currently under development. The preferences of the enzyme for substrates incorporating residues N-terminal to the cleavage site (P1, P2, etc.) have been elucidated, but little is known of its preferences for residues C-terminal to the cleavage site (P1′, P2′, etc.). The preferences of bovine factor Xa for substrate residues in the P1′, P2′ and P3′ positions were mapped using fluorescence-quenched substrates. Bovine factor Xa, often used as a model for factor Xa, was most selective for the P2′ position, less selective at the P1′ position and almost completely non-selective at the P3′ position. It appears that while the prime side subsites of factor Xa impose some selectivity towards substrates, the influence of these sites on factor Xa cleavage specificity is relatively low in comparison to related enzymes such as thrombin. |
| Databáze: | OpenAIRE |
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