3WQH

Crystal Structure of human DPP-IV in complex with Anagliptin

Summary for 3WQH

• Entry DOI: 10.2210/pdb3wqh/pdb
• Descriptor: Dipeptidyl peptidase 4, 2-acetamido-2-deoxy-beta-D-glucopyranose, N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide, ... (4 entities in total)
• Functional Keywords: diabetes, beta-propeller, aminopeptidase, membrane, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 172876.16

Authors

Watanabe, Y.S.,Okada, S.,Motoyama, T.,Takahashi, R.,Adachi, H.,Oka, M. (deposition date: 2014-01-27, release date: 2015-07-15, Last modification date: 2024-10-16)

Primary citation

Watanabe, Y.S.,Yasuda, Y.,Kojima, Y.,Okada, S.,Motoyama, T.,Takahashi, R.,Oka, M.
Anagliptin, a potent dipeptidyl peptidase IV inhibitor: its single-crystal structure and enzyme interactions.
J Enzyme Inhib Med Chem, 30:981-988, 2015

PubMed Abstract: The single-crystal structure of anagliptin, N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide, was determined. Two independent molecules were held together by intermolecular hydrogen bonds, and the absolute configuration of the 2-cyanopyrrolidine ring delivered from l-prolinamide was confirmed to be S. The interactions of anagliptin with DPP-4 were clarified by the co-crystal structure solved at 2.85 Å resolution. Based on the structure determined by X-ray crystallography, the potency and selectivity of anagliptin were discussed, and an SAR study using anagliptin derivatives was performed.

PubMed: 26147347
DOI: 10.3109/14756366.2014.1002402

Experimental method

X-RAY DIFFRACTION (2.85 Å)