- Tytuł:
- Theoretical studies of binding modes of two covalent inhibitors of cysteine proteases.
- Autorzy:
-
Drabik, Piotr
Politowska, Ewa
Czaplewski, Cezary
Kasprzykowski, Franciszek
Łankiewicz, Leszek
Ciarkowski, Jerzy - Powiązania:
- https://bibliotekanauki.pl/articles/1044228.pdf
- Data publikacji:
- 2000
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
cysteine proteases
covalent protease inhibitors
constrained simulated annealing
papain
molecular dynamics - Opis:
- Physiological and pathological roles of cysteine proteases make them important targets for inhibitor development. Although highly potent inhibitors of this group of enzymes are known, their major drawback is a lack of sufficient specificity. Two cysteine protease covalent inhibitors, viz. (i) Z-RL-deoxo-V-peptide-epoxysuccinyl hybrid, and (ii) Z-RLVG-methyl-, have been developed and modeled in the catalytic pocket of papain, an archetypal thiol protease. A number of configurations have been generated and relaxed for each system using the AMBER force field. The catalytic pockets S3 and S4 appear rather elusive in view of the observed inhibitors' flexibility. This suggest rather limited chances for the development of selective structure-based inhibitors of thiol proteases, designed to exploit differences in the structure of catalytic pockets of various members of this family.
- Źródło:
-
Acta Biochimica Polonica; 2000, 47, 4; 1061-1066
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł