5HDO

Crystal structure of a nanobody raised against urokinase-type plasminogen activator

5HDO の概要

• エントリーDOI: 10.2210/pdb5hdo/pdb
• 分子名称: Anti-HCV NS3/4A serine protease immoglobulin heavy chain, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: immune system
• 由来する生物種: Camelus dromedarius (Dromedary)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 54917.90

構造登録者

Kromann-Hansen, T. (登録日: 2016-01-05, 公開日: 2016-06-01, 最終更新日: 2024-11-13)

主引用文献

Kromann-Hansen, T.,Oldenburg, E.,Yung, K.W.,Ghassabeh, G.H.,Muyldermans, S.,Declerck, P.J.,Huang, M.,Andreasen, P.A.,Ngo, J.C.
A Camelid-derived Antibody Fragment Targeting the Active Site of a Serine Protease Balances between Inhibitor and Substrate Behavior.
J.Biol.Chem., 291:15156-15168, 2016

PubMed Abstract: A peptide segment that binds the active site of a serine protease in a substrate-like manner may behave like an inhibitor or a substrate. However, there is sparse information on which factors determine the behavior a particular peptide segment will exhibit. Here, we describe the first x-ray crystal structure of a nanobody in complex with a serine protease. The nanobody displays a new type of interaction between an antibody and a serine protease as it inserts its complementary determining region-H3 loop into the active site of the protease in a substrate-like manner. The unique binding mechanism causes the nanobody to behave as a strong inhibitor as well as a poor substrate. Intriguingly, its substrate behavior is incomplete, as 30-40% of the nanobody remained intact and inhibitory after prolonged incubation with the protease. Biochemical analysis reveals that an intra-loop interaction network within the complementary determining region-H3 of the nanobody balances its inhibitor versus substrate behavior. Collectively, our results unveil molecular factors, which may be a general mechanism to determine the substrate versus inhibitor behavior of other protease inhibitors.

PubMed: 27226628
DOI: 10.1074/jbc.M116.732503

実験手法

X-RAY DIFFRACTION (2.16 Å)