* Molecular dynamics and docking simulation of a natural variant of Activated Protein C with impaired protease activity: implications for integrin-mediated antiseptic function.
- Activated Protein C (APC) is a multifunctional serine protease, primarily known for its anticoagulant function in the coagulation system. Several studies have already elucidated its role in counteracting apoptosis and inflammation in cells, while significant effort is still ongoing for defining its involvement in sepsis. Earlier literature has shown that the antiseptic function of APC is mediated by its binding to leukocyte integrins, which is due to the presence of the integrin binding motif Arg-Gly-Asp at the N-terminus of the APC catalytic chain. Many natural mutants have been identified in patients with Protein C deficiency diagnosis including a variant of specificity pocket (Gly216Asp). In this work, we present a molecular model of the complex of APC with αVβ3 integrin obtained by protein-protein docking approach. A computational analysis of this variant is hereby presented, based on molecular dynamics and docking simulations, aiming at investigating the effects of the Gly216Asp mutation on the protein conformation and inferring its functional implications. Our study shows that such mutation is likely to impair the protease activity while preserving the overall protein fold. Moreover, superposition of the integrin binding motifs in wild-type and mutant forms suggests that the interaction with integrin can still occur and thus the mutant is likely to retain its antiseptic function related to the neutrophyl integrin binding. Therapeutic applications could result in this APC mutant which retains antiseptic function without anticoagulant side effects.
=>確認飛行物体;略:IFO
Overview of verb identify
The verb identify has 6 senses (first 6 from tagged texts)
1. (32) identify, place -- (recognize as being; establish the identity of someone or something; "She
identified the man on the 'wanted' poster")
2. (7) name, identify -- (give the name or identifying characteristics of; refer to by name or some
other identifying characteristic property; "Many senators were named in connection with the
scandal"; "The almanac identifies the auspicious months")
3. (6) identify -- (consider (oneself) as similar to somebody else; "He identified with the
refugees")
4. (4) identify -- (conceive of as united or associated; "Sex activity is closely identified with
the hypothalamus")
5. (2) identify, discover, key, key out, distinguish, describe, name -- (identify as in botany or
biology, for example)
6. (2) identify -- (consider to be equal or the same; "He identified his brother as one of the
fugitives")
Overview of adj identified
The adj identified has 1 sense (first 1 from tagged texts)
1. (1) identified -- (having the identity known or established; "the identified bodies were released
for burial")
--- WordNet end ---