2gjf

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(New page: 200px<br /><applet load="2gjf" size="350" color="white" frame="true" align="right" spinBox="true" caption="2gjf" /> '''NMR structure of the computationally designe...)
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[[Image:2gjf.gif|left|200px]]<br /><applet load="2gjf" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2gjf" />
 
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'''NMR structure of the computationally designed procarboxypeptidase-A (1AYE) domain'''<br />
 
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==Overview==
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==NMR structure of the computationally designed procarboxypeptidase-A (1AYE) domain==
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Recent efforts to design de novo or redesign the sequence and structure of, proteins using computational techniques have met with significant success., Most, if not all, of these computational methodologies attempt to model, atomic-level interactions, and hence high-resolution structural, characterization of the designed proteins is critical for evaluating the, atomic-level accuracy of the underlying design force-fields. We previously, used our computational protein design protocol RosettaDesign to completely, redesign the sequence of the activation domain of human, procarboxypeptidase A2. With 68% of the wild-type sequence changed, the, designed protein, AYEdesign, is over 10 kcal/mol more stable than the, wild-type protein. Here, we describe the high-resolution crystal structure, and solution NMR structure of AYEdesign, which show that the, experimentally determined backbone and side-chains conformations are, effectively superimposable with the computational model at atomic, resolution. To isolate the origins of the remarkable stabilization, we, have designed and characterized a new series of procarboxypeptidase, mutants that gain significant thermodynamic stability with a minimal, number of mutations; one mutant gains more than 5 kcal/mol of stability, over the wild-type protein with only four amino acid changes. We explore, the relationship between force-field smoothing and conformational sampling, by comparing the experimentally determined free energies of the overall, design and these focused subsets of mutations to those predicted using, modified force-fields, and both fixed and flexible backbone sampling, protocols.
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<StructureSection load='2gjf' size='340' side='right'caption='[[2gjf]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2gjf]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GJF FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gjf OCA], [https://pdbe.org/2gjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gjf RCSB], [https://www.ebi.ac.uk/pdbsum/2gjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gjf ProSAT]</span></td></tr>
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</table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gj/2gjf_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2gjf ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Recent efforts to design de novo or redesign the sequence and structure of proteins using computational techniques have met with significant success. Most, if not all, of these computational methodologies attempt to model atomic-level interactions, and hence high-resolution structural characterization of the designed proteins is critical for evaluating the atomic-level accuracy of the underlying design force-fields. We previously used our computational protein design protocol RosettaDesign to completely redesign the sequence of the activation domain of human procarboxypeptidase A2. With 68% of the wild-type sequence changed, the designed protein, AYEdesign, is over 10 kcal/mol more stable than the wild-type protein. Here, we describe the high-resolution crystal structure and solution NMR structure of AYEdesign, which show that the experimentally determined backbone and side-chains conformations are effectively superimposable with the computational model at atomic resolution. To isolate the origins of the remarkable stabilization, we have designed and characterized a new series of procarboxypeptidase mutants that gain significant thermodynamic stability with a minimal number of mutations; one mutant gains more than 5 kcal/mol of stability over the wild-type protein with only four amino acid changes. We explore the relationship between force-field smoothing and conformational sampling by comparing the experimentally determined free energies of the overall design and these focused subsets of mutations to those predicted using modified force-fields, and both fixed and flexible backbone sampling protocols.
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==About this Structure==
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High-resolution structural and thermodynamic analysis of extreme stabilization of human procarboxypeptidase by computational protein design.,Dantas G, Corrent C, Reichow SL, Havranek JJ, Eletr ZM, Isern NG, Kuhlman B, Varani G, Merritt EA, Baker D J Mol Biol. 2007 Mar 2;366(4):1209-21. Epub 2006 Dec 2. PMID:17196978<ref>PMID:17196978</ref>
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2GJF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GJF OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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High-resolution Structural and Thermodynamic Analysis of Extreme Stabilization of Human Procarboxypeptidase by Computational Protein Design., Dantas G, Corrent C, Reichow SL, Havranek JJ, Eletr ZM, Isern NG, Kuhlman B, Varani G, Merritt EA, Baker D, J Mol Biol. 2007 Mar 2;366(4):1209-21. Epub 2006 Dec 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17196978 17196978]
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</div>
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[[Category: ]]
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<div class="pdbe-citations 2gjf" style="background-color:#fffaf0;"></div>
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[[Category: Protein complex]]
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== References ==
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[[Category: Reichow, S.]]
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<references/>
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[[Category: designed protein]]
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__TOC__
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[[Category: procarboxypeptidase]]
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</StructureSection>
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[[Category: Large Structures]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 20:01:07 2008''
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[[Category: Reichow S]]

Current revision

NMR structure of the computationally designed procarboxypeptidase-A (1AYE) domain

PDB ID 2gjf

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