Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
444336 | Journal of Molecular Graphics and Modelling | 2012 | 9 Pages |
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.
Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (182 K)Download as PowerPoint slideHighlight► 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.