Ellis-Guardiola_2019_Biochemistry_58_1616

Reference

Title : Crystal Structure and Conformational Dynamics of Pyrococcus furiosus Prolyl Oligopeptidase - Ellis-Guardiola_2019_Biochemistry_58_1616
Author(s) : Ellis-Guardiola K , Rui H , Beckner RL , Srivastava P , Sukumar N , Roux B , Lewis JC
Ref : Biochemistry , 58 :1616 , 2019
Abstract :

Enzymes in the prolyl oligopeptidase family possess unique structures and substrate specificities that are important for their biological activity and for potential biocatalytic applications. The crystal structures of Pyrococcus furiosus ( Pfu) prolyl oligopeptidase (POP) and the corresponding S477C mutant were determined to 1.9 and 2.2 A resolution, respectively. The wild type enzyme crystallized in an open conformation, indicating that this state is readily accessible, and it contained bound chloride ions and a prolylproline ligand. These structures were used as starting points for molecular dynamics simulations of Pfu POP conformational dynamics. The simulations showed that large-scale domain opening and closing occurred spontaneously, providing facile substrate access to the active site. Movement of the loop containing the catalytically essential histidine into a conformation similar to those found in structures with fully formed catalytic triads also occurred. This movement was modulated by chloride binding, providing a rationale for experimentally observed activation of POP peptidase catalysis by chloride. Thus, the structures and simulations reported in this study, combined with existing biochemical data, provide a number of insights into POP catalysis.

PubMedSearch : Ellis-Guardiola_2019_Biochemistry_58_1616
PubMedID: 30786206
Gene_locus related to this paper: pyrfu-Q51714

Related information

Gene_locus pyrfu-Q51714
Structure 6CAN    5T88

Citations formats

Ellis-Guardiola K, Rui H, Beckner RL, Srivastava P, Sukumar N, Roux B, Lewis JC (2019)
Crystal Structure and Conformational Dynamics of Pyrococcus furiosus Prolyl Oligopeptidase
Biochemistry 58 :1616

Ellis-Guardiola K, Rui H, Beckner RL, Srivastava P, Sukumar N, Roux B, Lewis JC (2019)
Biochemistry 58 :1616