MCAD Medium Chain AcylCo A Dehydrogenase The Answer

MCAD Medium Chain Acyl-Co. A Dehydrogenase: The Answer to Some SIDS Cases Mount Mary College Students: Jessica Benson, Amy Ramirez, Nerissa Seward Faculty Advisor: Dr. Colleen Conway Medical College of Wisconsin Research Mentor: Dr. Jung-Ja Kim

Our Focus � � � Medim Chain Acyl-Coenzmye A dehydrogenase (MCAD) Flavin Adenine Dinucleotide (FAD) Electron Transferring Flavoprotein (ETF) Enzymes catalyzes the rate of reaction Multiple Intermolecular Interactions

MCAD

Degredation of Fatty Acids Substrate: Fatty Acid with ‘n’ number of carbons Enzyme: MCAD Product: Acyl. Coenzyme A Other Common Members of the Dehydrogenase Family: Very long chain Acyl-Co. A Long chain Acyl-Co. A Short chain Acyl-Co. A

MCAD Active Site � � � Accommodates substrates Binding the FAD Important Amino Acid � Glutamate-376 MCAD Substrat e Glu FAD Once the substrate is bound to the active site MCAD is able to catalyze the reaction

Flavin Adenine Dinucleotide � � � Function Isoalloxazine Ring Interactions

Electron Transfer between MCAD and FAD MCAD e e e FAD

Electron Transferring Flavoprotein � Structure and Interactions � FAD and 3 domains � ETF and MCAD Docking � Function � Accepts � and transports electrons Mutations � Electron transfer is inhibited

-Unbound ETF -Loop recognizes Hydrophobic Pocket of MCAD ETF FAD ETF e Leu e FAD MCAD FAD e MCAD -Bound ETF -Interactions between the Proteins Present -Electrons are transferred from MCAD to ETF

Our Focus Intermolecular Interactions Modeled in MCAD, FAD and ETF MCAD Active Site: Glu 376, Glu 199, Leu 103, Ser 142, Met 249, Asp 253, Arg 388 Folding of MCAD: 2 Dimers Combine: Arg 28: A and Glu 86: D Tetramer: Lys 304, Glu 300, Gln 342, Asp 346, Arg 383 FAD The following MCAD residues hydrogen bond to different atoms of FAD: Gln 380 Trp 166 Tyr 133 Thr 168 Thr 136 Ser 142 ETF Hydrogen Bonds: MCAD ETF Gly 60 and Leu 95 Thr 26 and Ala 193 Glu 34 and Tyr 192 Glu 22 and Thr 77 Ionic Interactions: MCAD ETF Glu 18 and Arg 76 Recognition Loop: Ile 14 to Ser 37

MCAD Deficiency � � � Autosomal recessive mutation Sudden Infant Death Syndrome (SIDS) Prevalence

MCAD Deficiency � � � Screening Symptoms Treatment

Future Research � � FAD Other Metabolic Disorders � Other members of the Acyl-Co. A Dehydrogenase family � Amino acid residues of MCAD

Acknowledgments � Center for Biomolecular Modeling � Dr. � Medical College of Wisconsin � Dr. � Margaret Franzen Jung-Ja Kim Mount Mary College � Sciences � Department National Science Foundation Grant � DUE-1022793