View source for 2kdm


==NMR structures of GA95 and GB95, two designed proteins with 95% sequence identity but different folds and functions==
<StructureSection load='2kdm' size='340' side='right'caption='[[2kdm]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kdm]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KDM 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kdm OCA], [https://pdbe.org/2kdm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kdm RCSB], [https://www.ebi.ac.uk/pdbsum/2kdm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kdm ProSAT]</span></td></tr>
</table>
== 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/kd/2kdm_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=2kdm ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We present here a structural and mechanistic description of how a protein changes its fold and function, mutation by mutation. Our approach was to create 2 proteins that (i) are stably folded into 2 different folds, (ii) have 2 different functions, and (iii) are very similar in sequence. In this simplified sequence space we explore the mutational path from one fold to another. We show that an IgG-binding, 4beta+alpha fold can be transformed into an albumin-binding, 3-alpha fold via a mutational pathway in which neither function nor native structure is completely lost. The stabilities of all mutants along the pathway are evaluated, key high-resolution structures are determined by NMR, and an explanation of the switching mechanism is provided. We show that the conformational switch from 4beta+alpha to 3-alpha structure can occur via a single amino acid substitution. On one side of the switch point, the 4beta+alpha fold is &gt;90% populated (pH 7.2, 20 degrees C). A single mutation switches the conformation to the 3-alpha fold, which is &gt;90% populated (pH 7.2, 20 degrees C). We further show that a bifunctional protein exists at the switch point with affinity for both IgG and albumin.

A minimal sequence code for switching protein structure and function.,Alexander PA, He Y, Chen Y, Orban J, Bryan PN Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21149-54. Epub 2009 Nov 18. PMID:19923431<ref>PMID:19923431</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2kdm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Alexander P]]
[[Category: Bryan P]]
[[Category: Chen Y]]
[[Category: He Y]]
[[Category: Orban J]]