Receptor binding and negative cooperativity of a mutant insulin, [LeuA3]-insulin.
[LeuA3]-insulin, the third mutant insulin, was semisynthesized and was studied for receptor binding and negative cooperative effects. Receptor binding and biological effects of the mutant insulin were 0.3-0.5% of normal, the lowest among three mutant insulins. However, negative cooperative effects of the mutant insulin were almost normal at higher concentration (greater than 10(-6) M). Monoclonal anti-insulin antibody binding studies revealed that carboxyterminal region of B chain was relatively unchanged. These results suggest that N-terminal region of A-chain extending to A3 is important for receptor binding and confirm that A3 does not play an important role for negative cooperativity.
D000273:Adipose Tissue / Q000378:metabolism; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D001667:Binding, Competitive; D003847:Deoxyglucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009154:Mutation; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013552:Swine
D007328:Insulin; D003847:Deoxyglucose; D011972:Receptor, Insulin