Inhibition of bovine beta-trypsin by the active site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azaornithine p-nitrophenyl ester: a kinetic and X-ray crystallographic study

Biochem Biophys Res Commun. 1995 Dec 14;217(2):437-44. doi: 10.1006/bbrc.1995.2795.

Abstract

Kinetics of the bovine beta-trypsin (trypsin) reaction with the active site titrant N alpha-(N,N-dimethylcarbamoyl)- alpha-aza-ornithine p-nitrophenyl ester (Dmc-azaOrn-ONp) was obtained at pH 6.2 and 21.0 degrees C. The results are consistent with the minimum three-step catalytic mechanism of serine proteinases involving a stable acyl.enzyme adduct. Dmc-azaOrn-ONp binds stoichiometrically to trypsin and allows the reliable determination of the active enzyme concentration between 1.0 x 10(-6) M and 3.0 x 10(-4) M. The three-dimensional structure of the trypsin.Dmc-azaOrn acyl.enzyme adduct has been solved by X-ray crystallography at 1.8 A resolution (R = 0.153). The Dmc-azaOrn moiety of the active site titrant is accommodated in the serine proteinase active center, occupying the S1 specificity subsite, and is covalently linked to the OG atom of the Ser195 catalytic residue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aza Compounds / chemistry*
  • Binding Sites
  • Cattle
  • Crystallography, X-Ray
  • Kinetics
  • Ornithine / analogs & derivatives*
  • Ornithine / chemistry
  • Solvents
  • Trypsin / chemistry*
  • Trypsin Inhibitors / chemistry*

Substances

  • Aza Compounds
  • Solvents
  • Trypsin Inhibitors
  • N-(alpha)-(N,N-dimethylcarbamoyl)-alpha-azaornithine 4-nitrophenyl ester
  • Ornithine
  • Trypsin