Relating Structure to Function in the Beta-Propeller Domain of Dipeptidyl Peptidase IV: Point mutations that influence adenosine deaminase binding, antibody binding and enzyme activity

Mark D. Gorrell, Catherine A. Abbott, Thilo Kähne, Miriam T. Levy, W. Bret Church, Geoffrey W. McCaughan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Point mutations in human CD26/DP IV were analysed for adenosine deaminase (ADA) binding, monoclonal antibody (mAb) binding and DP IV enzyme activity. Point mutations at either Leu294 or Va1341 ablated ADA binding. Binding by mAbs that inhibit ADA binding was found to involve both Leu340 to Arg343 and Thr440/Lys441. Glu205 and Glu206 were found to be essential for enzyme activity. All residues of interest were mapped onto a model of the β-propeller domain of DP IV. These data led us to suggest that in DP IV and related peptidases ligand and antibody binding sites are non-linear and that enzyme activity depends on charged sidechains that surround the entrance to the central tunnel of the β-propeller.

Original languageEnglish
Pages (from-to)89-95
Number of pages7
JournalAdvances in Experimental Medicine and Biology
Volume477
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Adenosine deaminase
  • Beta propeller
  • Dipeptidyl peptidase IV
  • Epitopes

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