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1his

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{{STRUCTURE_1his| PDB=1his | SCENE= }}
{{STRUCTURE_1his| PDB=1his | SCENE= }}
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'''STRUCTURE AND DYNAMICS OF DES-PENTAPEPTIDE-INSULIN IN SOLUTION: THE MOLTEN-GLOBULE HYPOTHESIS'''
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===STRUCTURE AND DYNAMICS OF DES-PENTAPEPTIDE-INSULIN IN SOLUTION: THE MOLTEN-GLOBULE HYPOTHESIS===
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==Overview==
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Structures of insulin in different crystal forms exhibit significant local and nonlocal differences, including correlated displacement of elements of secondary structure. Here we describe the solution structure and dynamics of a monomeric insulin analogue, des-pentapeptide-(B26-B30)-insulin (DPI), as determined by two-dimensional NMR spectroscopy and distance geometry/restrained molecular dynamics (DG/RMD). Although the solution structure of DPI exhibits a general similarity to its crystal structure, individual DG/RMD structures in the NMR ensemble differ by rigid-body displacements of alpha-helices that span the range of different crystal forms. These results suggest that DPI exists as a partially folded state formed by coalescence of distinct alpha-helix-associated microdomains. The physical reality of this model is investigated by comparison of the observed two-dimensional nuclear Overhauser enhancement (NOE) spectroscopy (NOESY) spectrum with that predicted from crystal and DG/RMD structures. The observed NOESY spectrum contains fewer tertiary contacts than predicted by any single simulation, but it matches their shared features; such "ensemble correspondence" is likely to reflect the effect of protein dynamics on observed NOE intensities. We propose (i) that the folded state of DPI is analogous to that of a compact protein-folding intermediate rather than a conventional native state and (ii) that the molten state is the biologically active species. This proposal (the molten-globule hypothesis) leads to testable thermodynamic predictions and has general implications for protein design.
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{{ABSTRACT_PUBMED_1549601}}
==About this Structure==
==About this Structure==
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1HIS 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=1HIS OCA].
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1HIS 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=1HIS 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 Tue Jul 1 08:14:26 2008''

Revision as of 05:14, 1 July 2008

Image:1his.png

Template:STRUCTURE 1his

STRUCTURE AND DYNAMICS OF DES-PENTAPEPTIDE-INSULIN IN SOLUTION: THE MOLTEN-GLOBULE HYPOTHESIS

Template:ABSTRACT PUBMED 1549601

About this Structure

1HIS is a Protein complex structure of sequences from Homo sapiens. Full experimental information is available from OCA.

Reference

Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis., Hua QX, Kochoyan M, Weiss MA, Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2379-83. PMID:1549601

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