کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
444336 | 692967 | 2012 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Coupled motions during dynamics reveal a tunnel toward the active site regulated by the N-terminal α-helix in an acylaminoacyl peptidase Coupled motions during dynamics reveal a tunnel toward the active site regulated by the N-terminal α-helix in an acylaminoacyl peptidase](/preview/png/444336.png)
Acylaminoacyl peptidase (AAP) subfamily belongs to the prolyl oligopeptidase (POP) family of serine-proteases. There is a great interest in the definition of molecular mechanisms related to the activity and substrate recognition of these complex multi-domain enzymes. The active site relies at the interface between the C-terminal catalytic domain and the β-propeller domain, whose N-terminal region acts as a bridge to the hydrolase domain. In AAP, the N-terminal extension is characterized by a structurally conserved α1-helix, which is known to affect thermal stability and thermal dependence of the catalytic activity. In the present contribution, results from hundreds nanosecond all-atom molecular dynamics simulations, along with analyses of the networks of cross-correlated motions of a member of the AAP subfamily are discussed. The MD investigation identifies a tunnel that from the surrounding of the N-terminal α1-helix bring to the catalytic site. This cavity seems to be regulated by conformational changes of the α1-helix itself during the dynamics. The evidence here provided can be a useful guide for a better understanding of the mechanistic aspects related to AAP activity, but also for drug design purposes.
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► Molecular dynamics simulations, cavity detection and coupled motions in a acylaminoacyl peptidase.
► Identification of a new tunnel toward the catalytic site and which can be modulate by conformational changes of the N-terminal α-helix.
► Interest for basic research on extremophilic enzyme but also for drug design purposes.
Journal: Journal of Molecular Graphics and Modelling - Volume 38, September 2012, Pages 226–234