8PI1

Bicyclic INCYPRO Pseudomonas fluorescens esterase

8PI1 の概要

• エントリーDOI: 10.2210/pdb8pi1/pdb
• 分子名称: Arylesterase, N-[2-[3,5-bis[2-(2-iodanylethanoylamino)ethanoyl]-1,3,5-triazinan-1-yl]-2-oxidanylidene-ethyl]-2-iodanyl-ethanamide, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: stabilization, cyclization, trimer, multimer, esterase, hydrolase
• 由来する生物種: Pseudomonas fluorescens
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 476051.14

構造登録者

Kiehstaller, S.,Pearce, N.M.,Grossmann, T.N.,Hennig, S. (登録日: 2023-06-20, 公開日: 2023-11-01, 最終更新日: 2024-11-06)

主引用文献

Hutchins, G.H.,Kiehstaller, S.,Poc, P.,Lewis, A.H.,Oh, J.,Sadighi, R.,Pearce, N.M.,Ibrahim, M.,Drienovska, I.,Rijs, A.M.,Neubacher, S.,Hennig, S.,Grossmann, T.N.
Covalent bicyclization of protein complexes yields durable quaternary structures.
Chem, 10:615-627, 2024

PubMed Abstract: Proteins are essential biomolecules and central to biotechnological applications. In many cases, assembly into higher-order structures is a prerequisite for protein function. Under conditions relevant for applications, protein integrity is often challenged, resulting in disassembly, aggregation, and loss of function. The stabilization of quaternary structure has proven challenging, particularly for trimeric and higher-order complexes, given the complexity of involved inter- and intramolecular interaction networks. Here, we describe the chemical bicyclization of homotrimeric protein complexes, thereby increasing protein resistance toward thermal and chemical stress. This approach involves the structure-based selection of cross-linking sites, their variation to cysteine, and a subsequent reaction with a triselectrophilic agent to form a protein assembly with bicyclic topology. Besides overall increased stability, we observe resistance toward aggregation and greatly prolonged shelf life. This bicyclization strategy gives rise to unprecedented protein chain topologies and can enable new biotechnological and biomedical applications.

PubMed: 38344167
DOI: 10.1016/j.chempr.2023.10.003

実験手法

X-RAY DIFFRACTION (2.5 Å)