1y4c: Difference between revisions

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-[[Image:1y4c.gif|left|200px]]<br /><applet load="1y4c" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1y4c, resolution 1.900&Aring;" />
-'''Designed Helical Protein fusion MBP'''<br />
-==Overview==
+==Designed Helical Protein fusion MBP==
-An IL-4 antagonist was designed based on structural and biochemical analysis of unbound IL-4 and IL-4 in complex with its high-affinity receptor (IL-4Ralpha). Our design strategy sought to capture a protein-protein interaction targeting the high affinity that IL-4 has for IL-4Ralpha. This strategy has impact due to the potential relevance of IL-4Ralpha as a drug target in the treatment of asthma. To mimic the IL-4 binding surface, critical side chains for receptor binding were identified, and these side chains were transplanted onto a previously characterized, de novo-designed four-helix protein called designed helical protein 1 (DHP-1). This first-generation design resolved the ambiguity previously described for the connectivity between helices in DHP-1 and resulted in a protein capable of binding to IL-4Ralpha. The second-generation antagonist was based upon further molecular modeling, and it succeeded in binding IL-4Ralpha better than the first-generation. This protein, termed DHP-14-AB, yielded a protein with a cooperative unfolding transition (DeltaGu0=8.1 kcal/mol) and an IC50 of 27 microM when in competition with IL-4 whereas DHP-1 had no affinity for IL-4Ralpha. The crystal structure of DHP-14-AB was determined to 1.9-A resolution and was compared with IL-4. This comparison revealed how design strategies targeting protein-protein interactions require high-resolution 3D data and the incorporation of orientation-specific information at the level of side-chains and secondary structure element interactions.
+<StructureSection load='1y4c' size='340' side='right'caption='[[1y4c]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[1y4c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y4C FirstGlance]. <br>
-Y4C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y4C OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene></td></tr>
-==Reference==
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1y4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y4c OCA], [https://pdbe.org/1y4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y4c RCSB], [https://www.ebi.ac.uk/pdbsum/1y4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y4c ProSAT]</span></td></tr>
-De novo design of an IL-4 antagonist and its structure at 1.9 A., Laporte SL, Forsyth CM, Cunningham BC, Miercke LJ, Akhavan D, Stroud RM, Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1889-94. Epub 2005 Jan 31. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15684085 15684085]
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.
+== 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/y4/1y4c_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=1y4c ConSurf].
+<div style="clear:both"></div>
+__TOC__
+</StructureSection>
 [[Category: Escherichia coli]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Akhavan, D.]]
+[[Category: Akhavan D]]
-[[Category: Cunningham, B C.]]
+[[Category: Cunningham BC]]
-[[Category: Forsyth, C M.]]
+[[Category: Forsyth CM]]
-[[Category: LaPorte, S L.]]
+[[Category: LaPorte SL]]
-[[Category: Miercke, L J.]]
+[[Category: Miercke LJ]]
-[[Category: Stroud, R M.]]
+[[Category: Stroud RM]]
-[[Category: de novo designed helical protein]]
-[[Category: maltose binding protein fusion]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:01:37 2008''