6RN6

DPP1 in complex with inhibitor

Summary for 6RN6

• Entry DOI: 10.2210/pdb6rn6/pdb
• Descriptor: Dipeptidyl peptidase 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (8 entities in total)
• Functional Keywords: dipeptidyl peptidase i, inhibitor complex, cathepsin c, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 80187.01

Authors

Kack, H. (deposition date: 2019-05-08, release date: 2019-08-28, Last modification date: 2024-11-06)

Primary citation

Kack, H.,Doyle, K.,Hughes, S.J.,Bodnarchuk, M.S.,Lonn, H.,Van De Poel, A.,Palmer, N.
DPP1 Inhibitors: Exploring the Role of Water in the S2 Pocket of DPP1 with Substituted Pyrrolidines.
Acs Med.Chem.Lett., 10:1222-1227, 2019

PubMed Abstract: A series of pyrrolidine amino nitrile DPP1 inhibitors have been developed and characterized. The S2 pocket structure-activity relationship for these compounds shows significant gains in potency for DPP1 from interacting further with target residues and a network of water molecules in the binding pocket. Herein we describe the X-ray crystal structures of several of these compounds alongside an analysis of factors influencing the inhibitory potency toward DPP1 of which stabilization of the water network, demonstrated using Grand Canonical Monte Carlo simulations and free energy calculations, is attributed as a main factor.

PubMed: 31413809
DOI: 10.1021/acsmedchemlett.9b00261

Experimental method

X-RAY DIFFRACTION (2.4 Å)