View source for 6y07


==Designing a Granulopoietic Protein by Topological Rescaffolding 1: Sohair==
<StructureSection load='6y07' size='340' side='right'caption='[[6y07]], [[NMR_Ensembles_of_Models | 19 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6y07]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y07 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Y07 FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6y07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y07 OCA], [http://pdbe.org/6y07 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6y07 RCSB], [http://www.ebi.ac.uk/pdbsum/6y07 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6y07 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Computational protein design is rapidly becoming more powerful, and improving the accuracy of computational methods would greatly streamline protein engineering by eliminating the need for empirical optimization in the laboratory. In this work, we set out to design novel granulopoietic agents using a rescaffolding strategy with the goal of achieving simpler and more stable proteins. All of the 4 experimentally tested designs were folded, monomeric, and stable, while the 2 determined structures agreed with the design models within less than 2.5 A. Despite the lack of significant topological or sequence similarity to their natural granulopoietic counterpart, 2 designs bound to the granulocyte colony-stimulating factor (G-CSF) receptor and exhibited potent, but delayed, in vitro proliferative activity in a G-CSF-dependent cell line. Interestingly, the designs also induced proliferation and differentiation of primary human hematopoietic stem cells into mature granulocytes, highlighting the utility of our approach to develop highly active therapeutic leads purely based on computational design.

Design of novel granulopoietic proteins by topological rescaffolding.,Hernandez Alvarez B, Skokowa J, Coles M, Mir P, Nasri M, Maksymenko K, Weidmann L, Rogers KW, Welte K, Lupas AN, Muller P, ElGamacy M PLoS Biol. 2020 Dec 22;18(12):e3000919. doi: 10.1371/journal.pbio.3000919., eCollection 2020 Dec. PMID:33351791<ref>PMID:33351791</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6y07" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct sequences]]
[[Category: Coles, M]]
[[Category: ElGamacy, M]]
[[Category: De novo protein]]
[[Category: Gcsf analog]]
[[Category: Protein design]]
[[Category: Receptor modulator]]