Dipeptidyl Peptidase IV, a Kidney Microvillus Serine Proteinase: Evidence for its Large Subunit Molecular Weight and Endopeptidase Activity

Abstract

Dipeptidyl peptidase IV was first described by Hopsu-Havu & Glenner (1966) and purified from kidney by Hopsu-Havu et al. (1968). Enzymes of this class (for a review, see McDonald et al., 1971) hydroylse dipeptides from the N-terminus of susceptible substrates. Barth et al. (1974) demonstrated that dipeptidyl peptidase IV exhibits two specificities, involving substrates of the types X-Pro-Y and X-Ala-Y, and that it is sensitive to inhibition by di-isopropyl phosphorofluoridate. The enzyme is one of a group of membrane-bound peptidases located in the microvilli of the proximal convoluted tubule (Booth & Kenny, 1974). Starting with pig kidney cortex, dipeptidyl peptidase IV was solubilized by autolysis at pH 3.8, and purified 300-fold by chromatography on columns of CM-cellulose, DEAEcellulose, Sepharose 6B and hydroxyapatite, each step being monitored by an assay using Gly-Pro-2-naphthylamide as substrate. The preparation moved as a single band on polyacrylamide-gel electrophoresis and appeared to be homogeneous in the analytical ultracentrifuge. When either the microvillus membrane (Booth & Kenny, 1976) or a portion of the solubilized extract at an early stage in the purification was labelled with di-isopropyl [32P]phosphorofluoridate, the only labelled protein was found to cochromatograph with the active enzyme.

Dipeptidyl peptidases 8 and 9: specificity and molecular characterization compared with dipeptidyl peptidase IV

“…The heterogenous S9b family of DPPs (dipeptidyl peptidases) is a growing family of serine peptidases, which is characterized by the first identified member DPP-IV (also called CD26; EC 3.4.14.5) [1]. DPP-IV was first identified by Hopsu-Havu and Glenner [2] as an enzyme that possesses a glycylproline β-naphthylamidase activity, and it was later shown that DPP-IV has a general ability to cleave prolyl and alanyl peptide bonds at the penultimate position from the N-terminus [3][4][5][6]. Initially, the observed specificity of DPP-IV was assumed to be unique, but other DPPs and related peptidases with similar specificity have since been identified [7,8].…”

Interaction of human dipeptidyl peptidase IV and human immunodeficiency virus type-1 transcription transactivator in Sf9 cells

“…DPPIV cleaves dipeptides from the N-terminus of oligopeptides with proline or alanine in their penultimate position [3,4]. Physiological substrates of DPPIV include chemokines, peptide hormones and neuropeptides.…”

Chapter 2. Marketed Small Molecule Dipeptidyl Peptidase IV (DPP4) Inhibitors as a New Class of Oral Anti-Diabetics

“…This protein was later identified as a serine protease that preferably cleaves prolyl and alanyl peptide bonds at the penultimate position from the N-terminus. [22][23][24] DPP4 is expressed as a glycoprotein on the surface of cells of most tissues, including kidney, liver, intestine, placenta, prostate, skin, lymphocytes, and endothelial cells. DPP4 is catalytically active as a dimer.…”