1a3p: Difference between revisions

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[[Image:1a3p.gif|left|200px]]
{{Seed}}
[[Image:1a3p.png|left|200px]]


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{{STRUCTURE_1a3p|  PDB=1a3p  |  SCENE=  }}  
{{STRUCTURE_1a3p|  PDB=1a3p  |  SCENE=  }}  


'''ROLE OF THE 6-20 DISULFIDE BRIDGE IN THE STRUCTURE AND ACTIVITY OF EPIDERMAL GROWTH FACTOR, NMR, 20 STRUCTURES'''
===ROLE OF THE 6-20 DISULFIDE BRIDGE IN THE STRUCTURE AND ACTIVITY OF EPIDERMAL GROWTH FACTOR, NMR, 20 STRUCTURES===




==Overview==
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Two synthetic analogues of murine epidermal growth factor, [Abu6, 20] mEGF4-48 (where Abu denotes amino-butyric acid) and [G1, M3, K21, H40] mEGF1-48, have been investigated by NMR spectroscopy. [Abu6, 20] mEGF4-48 was designed to determine the contribution of the 6-20 disulfide bridge to the structure and function of mEGF. The overall structure of this analogue was similar to that of native mEGF, indicating that the loss of the 6-20 disulfide bridge did not affect the global fold of the molecule. Significant structural differences were observed near the N-terminus, however, with the direction of the polypeptide chain between residues four and nine being altered such that these residues were now located on the opposite face of the main beta-sheet from their position in native mEGF. Thermal denaturation experiments also showed that the structure of [Abu6, 20] mEGF4-48 was less stable than that of mEGF. Removal of this disulfide bridge resulted in a significant loss of both mitogenic activity in Balb/c 3T3 cells and receptor binding on A431 cells compared with native mEGF and mEGF4-48, implying that the structural changes in [Abu6, 20] mEGF4-48, although limited to the N-terminus, were sufficient to interfere with receptor binding. The loss of binding affinity probably arose mainly from steric interactions of the dislocated N-terminal region with part of the receptor binding surface of EGF. [G1, M3, K21, H40] mEGF1-48 was also synthesized in order to compare the synthetic polypeptide with the corresponding product of recombinant expression. Its mitogenic activity in Balb/c 3T3 cells was similar to that of native mEGF and analysis of its 1H chemical shifts suggested that its structure was also very similar to native.
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{{ABSTRACT_PUBMED_10082370}}


==About this Structure==
==About this Structure==
1A3P is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A3P OCA].  
1A3P is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A3P OCA].  


==Reference==
==Reference==
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[[Category: Murine epidermal growth factor]]
[[Category: Murine epidermal growth factor]]
[[Category: Repeat]]
[[Category: Repeat]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 09:46:02 2008''
 
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Revision as of 12:56, 30 June 2008

File:1a3p.png

Template:STRUCTURE 1a3p

ROLE OF THE 6-20 DISULFIDE BRIDGE IN THE STRUCTURE AND ACTIVITY OF EPIDERMAL GROWTH FACTOR, NMR, 20 STRUCTURES

Template:ABSTRACT PUBMED 10082370

About this Structure

1A3P is a Single protein structure of sequence from Mus musculus. Full experimental information is available from OCA.

Reference

Role of the 6-20 disulfide bridge in the structure and activity of epidermal growth factor., Barnham KJ, Torres AM, Alewood D, Alewood PF, Domagala T, Nice EC, Norton RS, Protein Sci. 1998 Aug;7(8):1738-49. PMID:10082370

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