title: On a possible neutral charge state for the catalytic dyad in β-secretase when bound to hydroxyethylene transition state analogue inhibitors.
abstract: β-Secretase is one of the aspartic proteases involved in the formation of amyloid plaques in Alzheimer's disease patients. Our previous results using a combination of surface plasmon resonance experiments with molecular modeling calculations suggested that the Asp dyad in β-secretase bound to hydroxylethylene containing inhibitors adopts a neutral charged state. In this work, we show that the Asp dyad diprotonated state reproduced the binding ranking of a set of these inhibitors better than alternative protonation states.
authors: Departamento de Química Orgánica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors: Fredy
authors: F
authors: Sussman
authors: José M
authors: JM
authors: Otero
authors: M Carmen
authors: MC
authors: Villaverde
authors: Marian
authors: M
authors: Castro
authors: José L
authors: JL
authors: Domínguez
authors: Lucía
authors: L
authors: González-Louro
authors: Ramón J
authors: RJ
authors: Estévez
authors: J Carlos
authors: JC
authors: Estévez
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D002384:Catalysis; D005030:Ethylenes / Q000378:metabolism*; D006860:Hydrogen Bonding
chemical_list: D005030:Ethylenes; C067254:hydroxyethylene; D053829:Amyloid Precursor Protein Secretases