4PRO

ALPHA-LYTIC PROTEASE COMPLEXED WITH PRO REGION

4PRO の概要

• エントリーDOI: 10.2210/pdb4pro/pdb
• 分子名称: ALPHA-LYTIC PROTEASE (3 entities in total)
• 機能のキーワード: pro region, foldase, protein folding, serine protease
• 由来する生物種: Lysobacter enzymogenes; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75301.79

構造登録者

Sauter, N.K.,Mau, T.,Rader, S.D.,Agard, D.A. (登録日: 1998-10-01, 公開日: 1999-05-18, 最終更新日: 2023-08-09)

主引用文献

Sauter, N.K.,Mau, T.,Rader, S.D.,Agard, D.A.
Structure of alpha-lytic protease complexed with its pro region.
Nat.Struct.Biol., 5:945-950, 1998

PubMed Abstract: While the majority of proteins fold rapidly and spontaneously to their native states, the extracellular bacterial protease alpha-lytic protease (alphaLP) has a t(1/2) for folding of approximately 2,000 years, corresponding to a folding barrier of 30 kcal mol(-1). AlphaLP is synthesized as a pro-enzyme where its pro region (Pro) acts as a foldase to stabilize the transition state for the folding reaction. Pro also functions as a potent folding catalyst when supplied as a separate polypeptide chain, accelerating the rate of alphaLP folding by a factor of 3 x 10(9). In the absence of Pro, alphaLP folds only partially to a stable molten globule-like intermediate state. Addition of Pro to this intermediate leads to rapid formation of native alphaLP. Here we report the crystal structures of Pro and of the non-covalent inhibitory complex between Pro and native alphaLP. The C-shaped Pro surrounds the C-terminal beta-barrel domain of the folded protease, forming a large complementary interface. Regions of extensive hydration in the interface explain how Pro binds tightly to the native state, yet even more tightly to the folding transition state. Based on structural and functional data we propose that a specific structural element in alphaLP is largely responsible for the folding barrier and suggest how Pro can overcome this barrier.

PubMed: 9808037
DOI: 10.1038/2919

実験手法

X-RAY DIFFRACTION (2.4 Å)