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Atomic structure of the trypsin-A90720A complex: a unified approach to structure and function
A Y Lee1, T A Smitka, R Bonjouklian
1Department of Chemistry, Baker Laboratory, Cornell University, Ithaca, NY 14853-1301, USA.
Chemistry & Biology
|October 1, 1994
Summary
The three-dimensional structure of A90720A, a serine proteinase inhibitor from Microchaete loktakensis, bound to trypsin was determined. This reveals its absolute stereostructure and substrate-like inhibition mechanism.
Area of Science:
- Biochemistry
- Structural Biology
- Natural Products Chemistry
Background:
- A90720A is a potent serine proteinase inhibitor from the blue-green alga Microchaete loktakensis.
- Previous studies defined much of its structure but left stereochemistry and inhibition mechanisms unclear.
- The study aimed to elucidate the structure of A90720A in complex with trypsin.
Purpose of the Study:
- To determine the three-dimensional structure of the bovine trypsin-A90720A complex.
- To define the absolute stereostructure of A90720A.
- To understand the molecular basis of A90720A's inhibition of serine proteinases.
Main Methods:
- Crystallization of the bovine trypsin-A90720A complex.
- Single crystal X-ray diffraction analysis.
- Determination of the three-dimensional structure at 1.90 Å resolution.
Main Results:
- The three-dimensional structure of the complex was successfully determined.
- The absolute stereostructure of A90720A was defined.
- The bound conformation and mode of inhibition were elucidated.
Conclusions:
- A90720A inhibits trypsin in a substrate-like manner.
- Inhibition involves extensive hydrogen bonds, hydrophobic interactions, and steric complementarity.
- A90720A mimics canonical inhibitor conformations using mixed peptidal and nonpeptidal features.