Crystal Structures of the Inactive D30N Mutant of Feline Immunodeficiency Virus Protease Complexed with a Substrate and an Inhibitor

摘要: Crystal structures of complexes a D30N mutant feline immunodeficiency virus protease (FIV PR) complexed with statine-based inhibitor (LP-149), as well substrate based on modification this (LP-149S), have been solved and refined at resolutions 2.0 1.85 A, respectively. Both the are bound in active site similar mode, which also resembles mode binding LP-149 to native protease. The carbonyl oxygen scissile bond is not hydrated located within distance hydrogen an amido nitrogen atom from one two asparagines enzyme. 3.25 A conserved water molecule (Wat301). model tetrahedral intermediate enzyme was built by considering interactions observed all three crystal FIV PR. Molecular dynamics simulations wild-type PR were carried out, investigate final stages catalytic mechanism aspartic proteases.