title: Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates.
abstract: Atomic resolution structures of trypsin acyl-enzymes and a tetrahedral intermediate analog, along with previously solved structures representing the Michaelis complex, are used to reconstruct events in the catalytic cycle of this classic serine protease. Structural comparisons provide insight into active site adjustments involved in catalysis. Subtle motions of the catalytic serine and histidine residues coordinated with translation of the substrate reaction center are seen to favor the forward progress of the acylation reaction. The structures also clarify the attack trajectory of the hydrolytic water in the deacylation reaction.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Evette S
authors.initials: ES
authors.lastname: Radisky
authors.forename: Justin M
authors.initials: JM
authors.lastname: Lee
authors.forename: Chia-Jung Karen
authors.initials: CJ
authors.lastname: Lu
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Koshland
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D014357:Trypsin / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D012694:Serine; D006639:Histidine; D014357:Trypsin