Papaleo_2012_J.Mol.Graph.Model_38C_226

Reference

Title : Coupled motions during dynamics reveal a tunnel toward the active site regulated by the N-terminal alpha-helix in an acylaminoacyl peptidase - Papaleo_2012_J.Mol.Graph.Model_38C_226
Author(s) : Papaleo E , Renzetti G
Ref : J Mol Graph Model , 38C :226 , 2012
Abstract :

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 beta-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 alpha1-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 alpha1-helix bring to the catalytic site This cavity seems to be regulated by conformational changes of the alpha1-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.

PubMedSearch : Papaleo_2012_J.Mol.Graph.Model_38C_226
PubMedID: 23085164

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Citations formats

Papaleo E, Renzetti G (2012)
Coupled motions during dynamics reveal a tunnel toward the active site regulated by the N-terminal alpha-helix in an acylaminoacyl peptidase
J Mol Graph Model 38C :226

Papaleo E, Renzetti G (2012)
J Mol Graph Model 38C :226