1P01

Serine protease mechanism. structure of an inhibitory complex oF ALPHA-LYTIC Protease and a tightly bound peptide boronic acid

Summary for 1P01

• Entry DOI: 10.2210/pdb1p01/pdb
• Related PRD ID: PRD_000261
• Descriptor: ALPHA-LYTIC PROTEASE, N-(tert-butoxycarbonyl)-L-alanyl-N-[(1R)-1-(dihydroxyboranyl)-2-methylpropyl]-L-prolinamide, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Lysobacter enzymogenes
• Total number of polymer chains: 1
• Total formula weight: 20356.46

Authors

Bone, R.,Agard, D.A. (deposition date: 1989-04-24, release date: 1990-04-15, Last modification date: 2024-11-20)

Primary citation

Bone, R.,Shenvi, A.B.,Kettner, C.A.,Agard, D.A.
Serine protease mechanism: structure of an inhibitory complex of alpha-lytic protease and a tightly bound peptide boronic acid.
Biochemistry, 26:7609-7614, 1987

PubMed Abstract: The structure of the complex formed between alpha-lytic protease, a serine protease secreted by Lysobacter enzymogenes, and N-tert-butyloxycarbonylalanylprolylvaline boronic acid (Ki = 0.35 nM) has been studied by X-ray crystallography to a resolution of 2.0 A. The active-site serine forms a covalent, nearly tetrahedral adduct with the boronic acid moiety of the inhibitor. The complex is stabilized by seven hydrogen bonds between the enzyme and inhibitor with additional stabilization arising from van der Waals interactions between enzyme and inhibitor side chains and the burying of 330 A2 of hydrophobic surface area. Hydrogen bonding between Asp-102 and His-57 remains intact in the enzyme-inhibitor complex, and His N epsilon 2 is well positioned to donate its hydrogen to the leaving group. Little change in the positions of protease residues was observed on complex formation (root mean square main chain deviation = 0.13 A), suggesting that in its native state the enzyme is complementary to tetrahedral reaction intermediates or to the nearly tetrahedral transition state for the reaction.

PubMed: 3122831
DOI: 10.1021/bi00398a012

Experimental method

X-RAY DIFFRACTION (2 Å)