Two new cyclophilins from Fusarium sambucinum and Aspergillus niger: resistance of cyclophilin/cyclosporin A complexes against proteolysis.
Two new peptidyl-prolyl-cis/trans-isomerases were purified to homogeneity from Fusarium sambucinum and Aspergillus niger. They belong to the class of cyclosporin A binding proteins (cyclophilins) and have molecular masses of about 18 kDa. As has been shown for other cyclophilins, the isomerase activity of the enzymes is inhibited by cyclosporin A in the nanomolar range. Furthermore binding of cyclosporin A prevents proteolytic digestion of the cyclophilin/cyclosporin complexes by the endoproteases GluC, LysC and alpha-chymotrypsin, in contrast to the free cyclophilins, which are readily cleaved by these proteases. We could also observe this protection for cyclophilins from sheep thymus and from the cyclosporin producing fungus Tolypocladium inflatum.
Hornbogen
T
T
Institut für Biochemie und Molekulare Biologie, Technische Universität Berlin, Germany.
Pieper
R
R
Hoffmann
K
K
Kleinkauf
H
H
Zocher
R
R
D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors / Q000302:isolation & purification* / Q000378:metabolism; D000595:Amino Acid Sequence; D001234:Aspergillus niger / Q000201:enzymology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification* / Q000378:metabolism; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin / Q000378:metabolism; D016572:Cyclosporine / Q000378:metabolism* / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism; D005670:Fusarium / Q000201:enzymology*; D008666:Metalloendopeptidases; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019696:Peptidylprolyl Isomerase; D012697:Serine Endopeptidases / Q000378:metabolism
D002352:Carrier Proteins; D016572:Cyclosporine; D010450:Endopeptidases; D012697:Serine Endopeptidases; D002918:Chymotrypsin; C028344:glutamyl endopeptidase; D008666:Metalloendopeptidases; C039830:peptidyl-Lys metalloendopeptidase; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase