5VTA

Co-Crystal Structure of DPPIV with a Chemibody Inhibitor

5VTA の概要

• エントリーDOI: 10.2210/pdb5vta/pdb
• 関連するPDBエントリー: 4FFV 4FFW
• 分子名称: Dipeptidyl peptidase 4, Fab light chain, Fab heavy chain, ... (9 entities in total)
• 機能のキーワード: hydrolase, chemibody
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 535923.46

構造登録者

Wang, Z.,Johnstone, S.,Cheng, A. (登録日: 2017-05-16, 公開日: 2018-05-09, 最終更新日: 2024-11-13)

主引用文献

Cheng, A.C.,Doherty, E.M.,Johnstone, S.,DiMauro, E.F.,Dao, J.,Luthra, A.,Ye, J.,Tang, J.,Nixey, T.,Min, X.,Tagari, P.,Miranda, L.P.,Wang, Z.
Structure-guided Discovery of Dual-recognition Chemibodies.
Sci Rep, 8:7570-7570, 2018

PubMed Abstract: Small molecules and antibodies each have advantages and limitations as therapeutics. Here, we present for the first time to our knowledge, the structure-guided design of "chemibodies" as small molecule-antibody hybrids that offer dual recognition of a single target by both a small molecule and an antibody, using DPP-IV enzyme as a proof of concept study. Biochemical characterization demonstrates that the chemibodies present superior DPP-IV inhibition compared to either small molecule or antibody component alone. We validated our design by successfully solving a co-crystal structure of a chemibody in complex with DPP-IV, confirming specific binding of the small molecule portion at the interior catalytic site and the Fab portion at the protein surface. The discovery of chemibodies presents considerable potential for novel therapeutics that harness the power of both small molecule and antibody modalities to achieve superior specificity, potency, and pharmacokinetic properties.

PubMed: 29765112
DOI: 10.1038/s41598-018-25848-0

実験手法

X-RAY DIFFRACTION (2.8 Å)