The pancreas-specific protein disulphide-isomerase PDIp interacts with a hydroxyaryl group in ligands.
Using a cross-linking approach, we have recently demonstrated that radiolabelled model peptides or misfolded proteins specifically interact in vitro with two members of the protein disulphide- isomerase family, namely PDI and PDIp, in a crude extract from sheep pancreas microsomes. In addition, we have shown that tyrosine and tryptophan residues within a peptide are the recognition motifs for the binding to PDIp. Here we examine non-peptide ligands and present evidence that a hydroxyaryl group is a structural motif for the binding to PDIp; simple constructs containing this group and certain xenobiotics and phytoestrogens, which contain an unmodified hydroxyaryl group, can all efficiently inhibit peptide binding to PDIp. To our knowledge this is the first time that the recognition motif of a molecular chaperone or folding catalyst has been specified as a simple chemical structure.
Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK. p.klappa@ukc.ac.uk
P
P
Klappa
R B
RB
Freedman
M
M
Langenbuch
M S
MS
Lan
G K
GK
Robinson
L W
LW
Ruddock
D000818:Animals; D001665:Binding Sites; D003432:Cross-Linking Reagents / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D004968:Estrogens, Non-Steroidal / Q000378:metabolism; D007529:Isoflavones; D008024:Ligands; D008861:Microsomes / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology*; D010455:Peptides / Q000378:metabolism; D010636:Phenols / Q000378:metabolism; D048789:Phytoestrogens; D028321:Plant Preparations; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D014162:Transfection; D014439:Tyramine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D003432:Cross-Linking Reagents; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D008024:Ligands; D010455:Peptides; D010636:Phenols; D048789:Phytoestrogens; D028321:Plant Preparations; D014443:Tyrosine; D013004:Somatostatin; D012259:Ribonuclease, Pancreatic; D019704:Protein Disulfide-Isomerases; D014439:Tyramine