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Full-Text Articles in Life Sciences
Insights From Molecular Dynamics On Substrate Binding And Effects Of Active Site Mutations In Delta1-Pyrroline-5-Carboxylate Dehydrogenase, Bogdan F. Ion, Mohamed M. Aboelnga, James W. Gauld
Insights From Molecular Dynamics On Substrate Binding And Effects Of Active Site Mutations In Delta1-Pyrroline-5-Carboxylate Dehydrogenase, Bogdan F. Ion, Mohamed M. Aboelnga, James W. Gauld
Chemistry and Biochemistry Publications
The NAD+-dependent enzyme, 1-pyrroline-5-carboxylate dehydrogenase (P5CDH), has an important role in proline and hydroxyproline catabolism for humans. Specifically, this aldehyde dehydrogenase is responsible for the oxidation of both L-glutamate- -semialdehyde (GSA) and 4-erythro-hydroxy-L-glutamate- -semialdehyde (4-OH-GSA) to their respective L-glutamate product forms. We have performed a detailed molecular dynamics (MD) study of both the reactant and product complex structures of P5CDH to gain insights into ligand binding (i.e., GSA, 4-OH-GSA, NAD+, GLU) in the active site. Moreover, our investigations were further extended to examine the structural impact of S352L, S352A, and E314A mutations on the deficiency in the P5CDH enzymatic activity. …
Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion
Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion
STAR Program Research Presentations
Severe morbidity and mortality consequences result from irreversible inhibition of human acetylcholinesterase by organophosphates (OPs). Oxime-based reactivators are currently the only available treatments but lack efficacy in the central nervous system (CNS) where the most damage occurs. Computational docking and molecular dynamics (MD) simulations reveal complex structural barriers that may reduce oxime efficacy. These results may guide future drug designs of more effective countermeasures.