title: Structure of the RWJ-51084-bovine pancreatic beta-trypsin complex at 1.8 A.
abstract: The three-dimensional structure of bovine pancreatic trypsin complexed with the inhibitor RWJ-51084 has been determined at 1.8 A resolution. These crystals belong to the trigonal space group P3(1)21, with unit-cell parameters a = b = 53.43, c = 107.76 A. The refined R and R(free) values are 0.175 and 0.237, respectively. The carbonyl group bonded to the benzothiazole group of the inhibitor is covalently linked to the hydroxyl O atom of Ser195, forming a tetrahedral intermediate hemiketal structure. The other carbonyl O atom of the inhibitor forms a hydrogen bond with the Gln192 side-chain amide group. The benzothiazole group is oriented with the aromatic N atom of RWJ-51084 accepting a hydrogen bond from His57 NE2. The arginine side chain of the inhibitor extends into the deep and narrow pocket of the S1 specificity site of trypsin, forming a network of hydrogen bonds.
authors.affiliation: Center for Macromolecular Crystallography, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
authors.forename: R
authors.initials: R
authors.lastname: Recacha
authors.forename: M
authors.initials: M
authors.lastname: Carson
authors.forename: M J
authors.initials: MJ
authors.lastname: Costanzo
authors.forename: B
authors.initials: B
authors.lastname: Maryanoff
authors.forename: L J
authors.initials: LJ
authors.lastname: DeLucas
authors.forename: D
authors.initials: D
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry; D052160:Benzothiazoles; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010179:Pancreas / Q000201:enzymology; D017510:Protein Folding; D017433:Protein Structure, Secondary; D015842:Serine Proteinase Inhibitors / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*; D013917:Thrombin / Q000737:chemistry; D014357:Trypsin / Q000737:chemistry*; D014361:Trypsin Inhibitors / Q000737:chemistry
chemical_list: D052160:Benzothiazoles; C402796:RWJ 51084; D015842:Serine Proteinase Inhibitors; D013844:Thiazoles; D014361:Trypsin Inhibitors; D001120:Arginine; D014357:Trypsin; D013917:Thrombin