Structural analysis of the active site of porcine pancreatic elastase based on the X-ray crystal structures of complexes with trifluoroacetyl-dipeptide-anilide inhibitors. Academic Article uri icon

Overview

abstract

  • The X-ray crystal structures of two new (trifluoroacetyl)dipeptide p-(trifluoromethyl)anilide (TFA-dipeptide-TFM) inhibitors complexed to porcine pancreatic elastase are presented. TFA-Val-Ala-TFM and TFA-Phe-Ala-TFM both bind to elastase with the TFA group in the S1 subsite, Val or Phe in the S2 subsite, Ala in the S3 subsite, and the TFM group in the S4 subsite. Five other TFA-dipeptide-anilide/elastase crystal structures are available (two TFA-X-Ala-p-(trifluoromethyl)anilide, X = Lys, Leu, and three TFA-Lys-X-p-isopropylanilide, X = Pro, Leu, Phe). The four inhibitors with the trifluoromethyl substituent on the anilide ring bind in a single mode to elastase, whereas superposition of the three inhibitors with the isopropyl substituent on the anilide ring show three different modes of binding to the protein [Mattos, C., et al. (1994) Nature Struct. Biol. 1, 55-58]. The seven structures are taken together in a detailed analysis of the active site of porcine pancreatic elastase. The inhibition constants for the inhibitors are used in combination with the crystal structures to understand the specificity of the different elastase subsites.

publication date

  • March 14, 1995

Research

keywords

  • Dipeptides
  • Pancreatic Elastase

Identity

Scopus Document Identifier

  • 0028932309

Digital Object Identifier (DOI)

  • 10.1021/bi00010a008

PubMed ID

  • 7880814

Additional Document Info

volume

  • 34

issue

  • 10