title: Structural characterization of the papaya cysteine proteinases at low pH.
abstract: Current control of gastrointestinal nematodes relies primarily on the use of synthetic drugs and encounters serious problems of resistance. Oral administration of plant cysteine proteinases, known to be capable of damaging nematode cuticles, has recently been recommended to overcome these problems. This prompted us to examine if plant cysteine proteinases like the four papaya proteinases papain, caricain, chymopapain, and glycine endopeptidase that have been investigated here can survive acidic pH conditions and pepsin degradation. The four papaya proteinases have been found to undergo, at low pH, a conformational transition that instantaneously converts their native forms into molten globules that are quite unstable and rapidly degraded by pepsin. As shown by activity measurements, the denatured state of these proteinases which finally results from acid treatment is completely irreversible. It is concluded that cysteine proteinases from plant origin may require to be protected against both acid denaturation and proteolysis to be effective in the gut after oral administration.
authors.affiliation: Laboratoire de Chimie Générale (CP: 206/4), Institut de Pharmacie, Université Libre de Bruxelles, Campus de la Plaine, Boulevard du Triomphe, B-1050, Bruxelles, Belgique.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Huet
authors.forename: Yvan
authors.initials: Y
authors.lastname: Looze
authors.forename: Kristin
authors.initials: K
authors.lastname: Bartik
authors.forename: Vincent
authors.initials: V
authors.lastname: Raussens
authors.forename: René
authors.initials: R
authors.lastname: Wintjens
authors.forename: Paule
authors.initials: P
authors.lastname: Boussard
mesh_terms: D000284:Administration, Oral; D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D029441:Carica / Q000201:enzymology*; D002917:Chymopapain / Q000737:chemistry; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D010450:Endopeptidases / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D010940:Plant Proteins / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D000817:Anilino Naphthalenesulfonates; D010940:Plant Proteins; C027132:1-anilino-8-naphthalenesulfonate; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C039974:caricain; D002917:Chymopapain; D003545:Cysteine; D005998:Glycine