1hit

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[[Image:1hit.gif|left|200px]]
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{{Seed}}
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[[Image:1hit.png|left|200px]]
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{{STRUCTURE_1hit| PDB=1hit | SCENE= }}
{{STRUCTURE_1hit| PDB=1hit | SCENE= }}
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'''RECEPTOR BINDING REDEFINED BY A STRUCTURAL SWITCH IN A MUTANT HUMAN INSULIN'''
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===RECEPTOR BINDING REDEFINED BY A STRUCTURAL SWITCH IN A MUTANT HUMAN INSULIN===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_1961250}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 1961250 is the PubMed ID number.
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{{ABSTRACT_PUBMED_1961250}}
==About this Structure==
==About this Structure==
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1HIT is a [[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].
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1HIT is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HIT OCA].
==Reference==
==Reference==
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[[Category: Weiss, M A.]]
[[Category: Weiss, M A.]]
[[Category: Hormone]]
[[Category: Hormone]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:53:08 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 08:14:26 2008''

Revision as of 05:14, 1 July 2008

Image:1hit.png

Template:STRUCTURE 1hit

RECEPTOR BINDING REDEFINED BY A STRUCTURAL SWITCH IN A MUTANT HUMAN INSULIN

Template:ABSTRACT PUBMED 1961250

About this Structure

1HIT is a Protein complex structure of sequences from Homo sapiens. Full experimental information is available from 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:1961250

Page seeded by OCA on Tue Jul 1 08:14:26 2008

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