3W2T

Crystal structure of human depiptidyl peptidase IV (DPP-4) in complex with vildagliptin

3W2T の概要

• エントリーDOI: 10.2210/pdb3w2t/pdb
• 分子名称: Dipeptidyl peptidase 4, beta-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: alpha/beta, beta-propeller, hydrolase, aminopeptidase, serine protease, secreted, signal-anchor, transmembrane, diabetes, glycoprotein, cell membrane, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 176942.22

構造登録者

Kishida, H.,Nabeno, M.,Miyaguchi, I.,Tanaka, Y.,Katou, R.,Akahoshi, F. (登録日: 2012-12-04, 公開日: 2013-05-15, 最終更新日: 2024-10-30)

主引用文献

Nabeno, M.,Akahoshi, F.,Kishida, H.,Miyaguchi, I.,Tanaka, Y.,Ishii, S.,Kadowaki, T.
A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site
Biochem.Biophys.Res.Commun., 434:191-196, 2013

PubMed Abstract: In recent years, various dipeptidyl peptidase IV (DPP-4) inhibitors have been released as therapeutic drugs for type 2 diabetes in many countries. In spite of their diverse chemical structures, no comparative studies of their binding modes in the active site of DPP-4 have been disclosed. We determined the co-crystal structure of vildagliptin with DPP-4 by X-ray crystallography and compared the binding modes of six launched inhibitors in DPP-4. The inhibitors were categorized into three classes on the basis of their binding subsites: (i) vildagliptin and saxagliptin (Class 1) form interactions with the core S1 and S2 subsites and a covalent bond with Ser630 in the catalytic triad; (ii) alogliptin and linagliptin (Class 2) form interactions with the S1' and/or S2' subsites in addition to the S1 and S2 subsites; and (iii) sitagliptin and teneligliptin (Class 3) form interactions with the S1, S2 and S2 extensive subsites. The present study revealed that the additional interactions with the S1', S2' or S2 extensive subsite may increase DPP-4 inhibition beyond the level afforded by the fundamental interactions with the S1 and S2 subsites and are more effective than forming a covalent bond with Ser630.

PubMed: 23501107
DOI: 10.1016/j.bbrc.2013.03.010

実験手法

X-RAY DIFFRACTION (2.36 Å)