title: An oxyanion-hole selective serine protease inhibitor in complex with trypsin.
abstract: p-amidinophenylmethylphosphinic acid (AMPA) was designed, synthesized and crystallized in complex with trypsin to study interactions with the oxyanion hole at the S1 site. In comparison to benzamidine, AMPA shows improved activity, which the crystal structure demonstrates to result from hydrogen bonds between the negatively charged phosphinic acid group and the catalytic residues at the oxyanion hole.
authors.affiliation: Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago, 900 S. Ashland Avenue, M/C 870, Chicago, IL 60607-7173, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.forename: Fatima
authors.initials: F
authors.lastname: Marankan
authors.forename: Wentao
authors.initials: W
authors.lastname: Fu
authors.forename: David
authors.initials: D
authors.lastname: Crich
authors.forename: Andrew
authors.initials: A
authors.lastname: Mesecar
authors.forename: Michael E
authors.initials: ME
authors.lastname: Johnson
mesh_terms: D000838:Anions; D018360:Crystallography, X-Ray; D006801:Humans; D010721:Phosphinic Acids / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism*
chemical_list: D000838:Anions; D010721:Phosphinic Acids; D015842:Serine Proteinase Inhibitors; C448823:p-amidinophenylmethylphosphinic acid; D014357:Trypsin