1a3p: Difference between revisions
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'''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''' | ||
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[[Category: Norton, R.]] | [[Category: Norton, R.]] | ||
[[Category: Torres, A.]] | [[Category: Torres, A.]] | ||
[[Category: | [[Category: Disulfide connectivity]] | ||
[[Category: | [[Category: Egf-like domain]] | ||
[[Category: | [[Category: Growth factor]] | ||
[[Category: | [[Category: Murine epidermal growth factor]] | ||
[[Category: | [[Category: Repeat]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 09:46:02 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 09:46, 2 May 2008
ROLE OF THE 6-20 DISULFIDE BRIDGE IN THE STRUCTURE AND ACTIVITY OF EPIDERMAL GROWTH FACTOR, NMR, 20 STRUCTURES
OverviewOverview
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.
About this StructureAbout this Structure
1A3P is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Fri May 2 09:46:02 2008