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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'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_1549601}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 1549601 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_1549601}} |
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| ==About this Structure== | | ==About this Structure== |
| 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]. | | 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]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Weiss, M A.]] | | [[Category: Weiss, M A.]] |
| [[Category: Hormone]] | | [[Category: Hormone]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:53:07 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 08:14:26 2008'' |
