Investigating the Mechanisms of Active Site Mutations to the IT8G WT MCAD Protein to Better Understand Medium Chain Acyl--CoA Dehydrogenase Deficiency (MCADD)
Abstract
The human disorder Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) hinders β-oxidation (catabolizing one’s fats for energy), affecting approximately 1 in 17,000 people in the United States. Once mutated, the Acyl-CoA Dehydrogenase Medium-Chain (ACADM) gene, which is solely responsible for MCADD, is unable to produce enough MCAD enzymes to metabolize medium-chain fatty acids, causing fats to not catabolize, resulting in symptoms of lethargy and hypoglycemia, as well as damage to the brain and liver due to buildups of unused fatty tissue. The purpose of this project was to investigate the possible and known effects of different amino acid mutations on the human MediumChain Acyl-CoA Dehydrogenase (MCAD) protein and, utilizing bioinformatics software (PyMOL for modification, PyRx for computerized docking, LigPlot+ for active site identification, & Jmol for 3D printing), produce a color-coded 3D-printed model based on each mutation’s KM value to explain the molecular story and individual mutation effects of MCADD. This model builds on previous bioinformatics and in vivo experiments aimed at revealing the underlying enzymatic mechanisms of MCADD. The use of the 3D model was beneficial, enabling model viewers to locate, determine, and hypothesize the mutations and their effects on MCAD, in addition to providing a visual and physical learning aid for researchers, professors, students, and other biomedical professionals. Furthermore, the clarity produced by a physical model ultimately enables further research for MCADD and may assist in the development of a cure for those who unfortunately suffer from this rare condition.
Faculty Sponsors
Dr. Arthur Sikora, Dr. Emily Schmitt Lavin
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-5-2023 12:00 PM
End Date
4-6-2023 4:00 PM
Investigating the Mechanisms of Active Site Mutations to the IT8G WT MCAD Protein to Better Understand Medium Chain Acyl--CoA Dehydrogenase Deficiency (MCADD)
Alvin Sherman Library
The human disorder Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) hinders β-oxidation (catabolizing one’s fats for energy), affecting approximately 1 in 17,000 people in the United States. Once mutated, the Acyl-CoA Dehydrogenase Medium-Chain (ACADM) gene, which is solely responsible for MCADD, is unable to produce enough MCAD enzymes to metabolize medium-chain fatty acids, causing fats to not catabolize, resulting in symptoms of lethargy and hypoglycemia, as well as damage to the brain and liver due to buildups of unused fatty tissue. The purpose of this project was to investigate the possible and known effects of different amino acid mutations on the human MediumChain Acyl-CoA Dehydrogenase (MCAD) protein and, utilizing bioinformatics software (PyMOL for modification, PyRx for computerized docking, LigPlot+ for active site identification, & Jmol for 3D printing), produce a color-coded 3D-printed model based on each mutation’s KM value to explain the molecular story and individual mutation effects of MCADD. This model builds on previous bioinformatics and in vivo experiments aimed at revealing the underlying enzymatic mechanisms of MCADD. The use of the 3D model was beneficial, enabling model viewers to locate, determine, and hypothesize the mutations and their effects on MCAD, in addition to providing a visual and physical learning aid for researchers, professors, students, and other biomedical professionals. Furthermore, the clarity produced by a physical model ultimately enables further research for MCADD and may assist in the development of a cure for those who unfortunately suffer from this rare condition.
