Disease-Associated Mutations Impact DNA Methyltransferase 1 Function through Dynamic Allosteric Effects and Solvent Exposure.

Abstract excerpt

Mutations in the DNA methyltransferase 1 (DNMT1) enzyme can lead to neurodegenerative diseases, including autosomal dominant cerebellar ataxia-deafness and neuropathy (ADCA-DN) and hereditary sensory and autonomic neuropathy type 1E (HSAN1E). The impact of these mutations on the structural dynamics of DNMT1 remains largely unknown. Here, we present an extensive molecular dynamics investigation of wild-type (WT)...

Topics

• Humans
• Molecular Dynamics Simulation
• Mutation
• Allosteric Regulation
• DNA (Cytosine-5-)-Methyltransferase 1
• Solvents