Comparison of a molecular dynamics model with the X-ray structure of the N370S acid-beta-glucosidase mutant that causes Gaucher disease.

Abstract

Recently, two studies were published that examined the structure of the acid-β-glucosidase N370S mutant, the most common mutant that causes Gaucher disease. One study used the experimental tool of X-ray crystallography, and the other utilized molecular dynamics (MD). The two studies reinforced each other through the similarities in their findings, but each approach also added some unique information. Both studies report that the conformation of active site loop 3 changes, due to an altered hydrogen bonding network; however, the MD study produced additional data concerning the flexibility of loop 1 and the catalytic residues that are not observed in the other study.

• Authors: Marc N Offman, Marcin Krol, Burkhard Rost, Israel Silman, Joel L Sussman, Anthony H Futerman
• Journal: Protein engineering, design & selection : PEDS (Protein Eng Des Sel) Vol. 24 Issue 10 Pg. 773-5 (Oct 2011) ISSN: 1741-0134 [Electronic] England
• PMID: 21724649 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucosylceramidase

Topics

• Animals
• Catalysis
• Crystallography, X-Ray (methods)
• Gaucher Disease (enzymology, genetics, metabolism)
• Glucosylceramidase (chemistry, genetics, metabolism)
• Humans
• Hydrogen Bonding
• Molecular Dynamics Simulation
• Mutation