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Domain flexibility in aspartic proteinases.
A Sali1, B Veerapandian, J B Cooper
1Department of Crystallography, Birkbeck College, University of London, England.
Proteins
|February 1, 1992
Summary
Endothiapepsin exists in two structural forms, allowing domains to move as rigid bodies. This movement alters the active site cleft shape, affecting how inhibitors bind and influencing aspartic proteinase hydrolysis models.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Endothiapepsin (EC 3.4.23.6) is an aspartic proteinase.
- Aspartic proteinases play crucial roles in biological processes.
- Understanding enzyme structure-function relationships is vital.
Purpose of the Study:
- To compare the three-dimensional structures of native endothiapepsin and its inhibitor complexes.
- To investigate the dynamic movement of endothiapepsin domains.
- To elucidate the impact of structural changes on active site conformation and inhibitor binding.
Main Methods:
- High-resolution X-ray crystallography was used to determine structures.
- Comparison of multiple endothiapepsin-inhibitor complexes.
- Rigid body analysis and translational, librational, and screw (TLS) analysis of thermal parameters.
Main Results:
- Endothiapepsin exhibits two distinct structural forms due to domain reorientation (residues 190-302).
- Domains move as rigid bodies with limited inter-domain interactions.
- Structural changes result in altered active site cleft shape, particularly the S3 pocket, influencing inhibitor binding.
Conclusions:
- The enzyme's flexibility allows for rigid body movements between domains.
- These movements are critical for understanding aspartic proteinase mechanisms.
- The findings provide insights into enzyme-inhibitor interactions and hydrolysis models.