7xl0
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Vobarilizumab at 1.70 Angstrom== | |
| + | <StructureSection load='7xl0' size='340' side='right'caption='[[7xl0]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7xl0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XL0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XL0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7xl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xl0 OCA], [https://pdbe.org/7xl0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xl0 RCSB], [https://www.ebi.ac.uk/pdbsum/7xl0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xl0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The camelid single domain antibody, referred to VHH or Nanobody, is considered a versatile tool for various biotechnological and clinical applications because of its favorable biophysical properties. To take advantage of these characteristics and for its application in biotechnology and therapy, research on VHH engineering is currently vigorously conducted. To humanize a camelid VHH, we performed complementarity determining region (CDR) grafting using a humanized VHH currently in clinical trials, and investigated the effects of these changes on the biophysical properties of the resulting VHH. The chimeric VHH exhibited a significant decrease in affinity and thermal stability and a large conformational change in the CDR3. To elucidate the molecular basis for these changes, we performed mutational analyses on the framework regions revealing the contribution of individual residues within the framework region. It is demonstrated that the mutations resulted in the loss of affinity and lower thermal stability, revealing the significance of bulky residues in the vicinity of the CDR3, and the importance of intramolecular interactions between the CDR3 and the framework-2 region. Subsequently, we performed back-mutational analyses on the chimeric VHH. Back-mutations resulted in an increase of the thermal stability and affinity. These data suggested that back-mutations restored the intramolecular interactions, and proper positioning and/or dynamics of the CDR3, resulting in the gain of thermal stability and affinity. These observations revealed the molecular contribution of the framework region on VHHs and further designability of the framework region of VHHs without modifying the CDRs. | ||
| - | + | Molecular basis for thermal stability and affinity in a VHH: Contribution of the framework region and its influence in the conformation of the CDR3.,Kinoshita S, Nakakido M, Mori C, Kuroda D, Caaveiro JMM, Tsumoto K Protein Sci. 2022 Nov;31(11):e4450. doi: 10.1002/pro.4450. PMID:36153698<ref>PMID:36153698</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7xl0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Lama glama]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Caaveiro JMM]] | ||
| + | [[Category: Kinoshita S]] | ||
| + | [[Category: Mori C]] | ||
| + | [[Category: Nakakido M]] | ||
| + | [[Category: Tsumoto K]] | ||
Revision as of 07:27, 9 November 2022
Crystal structure of Vobarilizumab at 1.70 Angstrom
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