An analysis of subdomain orientation, conformational change and disorder in relation to crystal packing of aspartic proteinases

The analysis reported here describes detailed structural studies of endothiapepsin (the aspartic proteinase from Endothia parasitica), with and without bound inhibitors, and human pepsin 3b. Comparison of multiple crystal structures of members of the aspartic proteinase family has revealed small but...

Full description

Saved in:
Bibliographic Details
Published in:Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2012-05, Vol.68 (5), p.541-552
Main Authors: Bailey, D., Carpenter, E. P., Coker, A., Coker, S., Read, J., Jones, A. T., Erskine, P., Aguilar, C. F., Badasso, M., Toldo, L., Rippmann, F., Sanz-Aparicio, J., Albert, A., Blundell, T. L., Roberts, N. B., Wood, S. P., Cooper, J. B.
Format: Article
Language:English
Subjects:
Ascomycota - enzymology
Aspartic Acid Endopeptidases - antagonists & inhibitors
Aspartic Acid Endopeptidases - chemistry
Aspartic Acid Proteases - antagonists & inhibitors
Aspartic Acid Proteases - chemistry
aspartic proteinases
crystal packing
Crystal structure
Crystallography, X-Ray
endothiapepsin
Enzymes
Flexibility
Human
Humans
Inhibitors
Models, Molecular
Movements
Orientation
Pepsin
Pepsin A - antagonists & inhibitors
Pepsin A - chemistry
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacology
Protein Conformation
Protein Structure, Tertiary
Proteinase
Proteins
subdomain orientation
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The analysis reported here describes detailed structural studies of endothiapepsin (the aspartic proteinase from Endothia parasitica), with and without bound inhibitors, and human pepsin 3b. Comparison of multiple crystal structures of members of the aspartic proteinase family has revealed small but significant differences in domain orientation in different crystal forms. In this paper, it is shown that these differences in domain orientation do not necessarily correlate with the presence or absence of bound inhibitors, but appear to stem at least partly from crystal contacts mediated by sulfate ions. However, since the same inherent flexibility of the structure is observed for other enzymes in this family such as human pepsin, the native structure of which is also reported here, the observed domain movements may well have implications for the mechanism of catalysis.
ISSN:1399-0047
0907-4449
1399-0047
DOI:10.1107/S0907444912004817