6CAN
Prolyl oligopeptidase mutant S477C from Pyrococcus furiosus
Summary for 6CAN
| Entry DOI | 10.2210/pdb6can/pdb |
| Related | 5T88 |
| Descriptor | Prolyl endopeptidase, CHLORIDE ION (3 entities in total) |
| Functional Keywords | prolyl oligopeptidase, hyperthermostable, alpha/beta hydrolase, peptidase, hydrolase |
| Biological source | Pyrococcus furiosus |
| Total number of polymer chains | 2 |
| Total formula weight | 142086.94 |
| Authors | Ellis-Guardiola, K.,Lewis, J.C.,Sukumar, N. (deposition date: 2018-01-31, release date: 2019-02-06, Last modification date: 2023-10-04) |
| Primary citation | Ellis-Guardiola, K.,Rui, H.,Beckner, R.L.,Srivastava, P.,Sukumar, N.,Roux, B.,Lewis, J.C. Crystal Structure and Conformational Dynamics of Pyrococcus furiosus Prolyl Oligopeptidase. Biochemistry, 58:1616-1626, 2019 Cited by PubMed 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 Å 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. PubMed: 30786206DOI: 10.1021/acs.biochem.9b00031 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
Download full validation report
