Abstract |
The disruption of aspartoacylase enzyme's catalytic activity causes fatal neurodegenerative Canavan disease. By molecular dynamics and docking methods, here we studied two deleterious mutations that have been identified in the Canavan patients' genotype E285A, F295S, and revealed the possible cause for the enzyme inhibition due to the drastic changes in active site dynamics, loss of interactions among Arg 71, Arg 168 and the substrate and pKa value of critical Glu178 residue. In addition to changes in the enzyme dynamics, free energy calculations show that the binding energy of substrate decreases dramatically up on mutations.
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Authors | Abdulkadir Kocak, Muslum Yildiz |
Journal | Journal of molecular graphics & modelling
(J Mol Graph Model)
Vol. 74
Pg. 44-53
(06 2017)
ISSN: 1873-4243 [Electronic] United States |
PMID | 28349879
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 Elsevier Inc. All rights reserved. |
Chemical References |
- Aspartic Acid
- N-acetylaspartate
- Amidohydrolases
- aspartoacylase
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Topics |
- Amidohydrolases
(chemistry, genetics)
- Aspartic Acid
(analogs & derivatives, chemistry)
- Canavan Disease
(enzymology, genetics)
- Catalytic Domain
- Humans
- Hydrogen Bonding
- Molecular Docking Simulation
- Molecular Dynamics Simulation
- Mutation, Missense
- Protein Binding
- Thermodynamics
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