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'''RECEPTOR BINDING REDEFINED BY A STRUCTURAL SWITCH IN A MUTANT HUMAN INSULIN'''<br />

==Overview==
Crystal structures of insulin have been determined in various distinct forms, the relevance of which to receptor recognition has long been the subject of speculation. Recently the crystal structure of an inactive insulin analogue has been determined and, surprisingly, found to have a conformation identical to native insulin. On this basis Dodson and colleagues have suggested that the known insulin crystal structures reflect an inactive conformation, and that a change in conformation is required for activity--specifically, the carboxy terminal residues of the B-chain are proposed to separate from the amino terminal residues of the A-chain. Here we report the solution structure of an active insulin mutant, determined by two-dimensional NMR, which supports this hypothesis. In the mutant, the carboxy terminal beta-turn and beta-strand of the B-chain are destabilized and do not pack across the rest of the molecule. We suggest that analogous detachment of the carboxy terminal region of the B-chain occurs in native insulin on binding to its receptor. Our finding that partial unfolding of the B-chain exposes an alternative protein surface rationalizes the receptor-binding properties of a series of anomalous insulin analogues, including a mutant insulin associated with diabetes mellitus in man.

==Disease==
Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], Hyperproinsulinemia, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], MODY, one form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]]

==About this Structure==
1HIT is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HIT OCA]. 

==Reference==
Receptor binding redefined by a structural switch in a mutant human insulin., Hua QX, Shoelson SE, Kochoyan M, Weiss MA, Nature. 1991 Nov 21;354(6350):238-41. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=1961250 1961250]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Hua, Q X.]]
[[Category: Kochoyan, M.]]
[[Category: Weiss, M A.]]
[[Category: hormone]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:01:40 2008''