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Full-Text Articles in Chemistry
Molecular Determinants Of Substrate Specificity In Human Insulin-Degrading Enzyme, Lazaros Stefanidis, Nicholas D. Fusco, Samantha E. Cooper, Jilian E. Smith-Carpenter, Benjamin J. Alper
Molecular Determinants Of Substrate Specificity In Human Insulin-Degrading Enzyme, Lazaros Stefanidis, Nicholas D. Fusco, Samantha E. Cooper, Jilian E. Smith-Carpenter, Benjamin J. Alper
Chemistry & Physics Faculty Publications
Insulin-degrading enzyme (IDE) is a 110 kDa chambered zinc metalloendopeptidase that degrades insulin, amyloid beta, and other intermediate-sized aggregation prone peptides that adopt β-structures. Structural studies of IDE in complex with multiple physiological substrates have suggested a role for hydrophobic and aromatic residues of the IDE active site in substrate binding and catalysis. Here, we examine functional requirements for conserved hydrophobic and aromatic IDE active site residues that are positioned within 4.5 Angstroms of IDE bound insulin B chain and amyloid beta peptides in the reported crystal structures for the respective enzyme-substrate complexes. Charge, size, hydrophobicity, aromaticity, and other functional …