4PRO

ALPHA-LYTIC PROTEASE COMPLEXED WITH PRO REGION

Summary for 4PRO

• Entry DOI: 10.2210/pdb4pro/pdb
• Descriptor: ALPHA-LYTIC PROTEASE (3 entities in total)
• Functional Keywords: pro region, foldase, protein folding, serine protease
• Biological source: Lysobacter enzymogenes; More
• Total number of polymer chains: 4
• Total formula weight: 75301.79

Authors

Sauter, N.K.,Mau, T.,Rader, S.D.,Agard, D.A. (deposition date: 1998-10-01, release date: 1999-05-18, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)