View source for 4yaq


==Crystal structure of a computationally optimized PG9 mutant==
<StructureSection load='4yaq' size='340' side='right'caption='[[4yaq]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yaq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YAQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</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=4yaq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yaq OCA], [https://pdbe.org/4yaq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yaq RCSB], [https://www.ebi.ac.uk/pdbsum/4yaq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yaq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6GMW3_HUMAN Q6GMW3_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Several HIV envelope-targeting (Env-targeting) antibodies with broad and potent neutralizing activity have been identified and shown to have unusual features. Of these, the PG9 antibody has a long heavy chain complementarity determining region 3 (HCDR3) and possesses unique structural elements that interact with protein and glycan features of the HIV Env glycoprotein. Here, we used the Rosetta software suite to design variants of the PG9 antibody HCDR3 loop with the goal of identifying variants with increased potency and breadth of neutralization for diverse HIV strains. One variant, designated PG9_N100FY, possessed increased potency and was able to neutralize a diverse set of PG9-resistant HIV strains, including those lacking the Env N160 glycan, which is critical for PG9 binding. An atomic resolution structure of the PG9_N100FY fragment antigen binding (Fab) confirmed that the mutated residue retains the paratope surface when compared with WT PG9. Differential scanning calorimetry experiments revealed that the mutation caused a modest increase in thermodynamic stability of the Fab, a feature predicted by the computational model. Our findings suggest that thermodynamic stabilization of the long HCDR3 in its active conformation is responsible for the increased potency of PG9_N100FY, and strategies aimed at stabilizing this region in other HIV antibodies could become an important approach to in silico optimization of antibodies.

Redesigned HIV antibodies exhibit enhanced neutralizing potency and breadth.,Willis JR, Sapparapu G, Murrell S, Julien JP, Singh V, King HG, Xia Y, Pickens JA, LaBranche CC, Slaughter JC, Montefiori DC, Wilson IA, Meiler J, Crowe JE Jr J Clin Invest. 2015 Jun 1;125(6):2523-31. doi: 10.1172/JCI80693. Epub 2015 May, 18. PMID:25985274<ref>PMID:25985274</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4yaq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Julien JP]]
[[Category: Murrell S]]
[[Category: Wilson IA]]