1a3p: Difference between revisions

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New page: left|200px<br /><applet load="1a3p" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a3p" /> '''ROLE OF THE 6-20 DISULFIDE BRIDGE IN THE STR...
 
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[[Image:1a3p.gif|left|200px]]<br /><applet load="1a3p" size="450" color="white" frame="true" align="right" spinBox="true"
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'''ROLE OF THE 6-20 DISULFIDE BRIDGE IN THE STRUCTURE AND ACTIVITY OF EPIDERMAL GROWTH FACTOR, NMR, 20 STRUCTURES'''<br />


==Overview==
==ROLE OF THE 6-20 DISULFIDE BRIDGE IN THE STRUCTURE AND ACTIVITY OF EPIDERMAL GROWTH FACTOR, NMR, 20 STRUCTURES==
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.
<StructureSection load='1a3p' size='340' side='right'caption='[[1a3p]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1a3p]] is a 1 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A3P FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1a3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a3p OCA], [https://pdbe.org/1a3p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a3p RCSB], [https://www.ebi.ac.uk/pdbsum/1a3p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a3p ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/EGF_MOUSE EGF_MOUSE] EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6 (By similarity).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a3/1a3p_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1a3p ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1A3P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A3P OCA].
*[[Epidermal growth factor|Epidermal growth factor]]
 
__TOC__
==Reference==
</StructureSection>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10082370 10082370]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Alewood D]]
[[Category: Alewood, D.]]
[[Category: Alewood P]]
[[Category: Alewood, P.]]
[[Category: Barnham K]]
[[Category: Barnham, K.]]
[[Category: Domagala T]]
[[Category: Domagala, T.]]
[[Category: Nice E]]
[[Category: Nice, E.]]
[[Category: Norton R]]
[[Category: Norton, R.]]
[[Category: Torres A]]
[[Category: Torres, A.]]
[[Category: disulfide connectivities]]
[[Category: egf-like domain]]
[[Category: growth factor]]
[[Category: murine epidermal growth factor]]
[[Category: repeat]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 10:35:22 2007''

Latest revision as of 18:20, 13 March 2024

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

Structural highlights

1a3p is a 1 chain structure with sequence from Mus musculus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EGF_MOUSE EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6 (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

Drag the structure with the mouse to rotate

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