2b2x: Difference between revisions
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< | ==VLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 Fab== | ||
<StructureSection load='2b2x' size='340' side='right'caption='[[2b2x]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2b2x]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B2X 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]] 2.2Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2b2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b2x OCA], [https://pdbe.org/2b2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b2x RCSB], [https://www.ebi.ac.uk/pdbsum/2b2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b2x ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ITA1_RAT ITA1_RAT] Integrin alpha-1/beta-1 is a receptor for laminin and collagen. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. | |||
== 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/b2/2b2x_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=2b2x ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Improving the affinity of a high-affinity protein-protein interaction is a challenging problem that has practical applications in the development of therapeutic biomolecules. We used a combination of structure-based computational methods to optimize the binding affinity of an antibody fragment to the I-domain of the integrin VLA1. Despite the already high affinity of the antibody (Kd approximately 7 nM) and the moderate resolution (2.8 A) of the starting crystal structure, the affinity was increased by an order of magnitude primarily through a decrease in the dissociation rate. We determined the crystal structure of a high-affinity quadruple mutant complex at 2.2 A. The structure shows that the design makes the predicted contacts. Structural evidence and mutagenesis experiments that probe a hydrogen bond network illustrate the importance of satisfying hydrogen bonding requirements while seeking higher-affinity mutations. The large and diverse set of interface mutations allowed refinement of the mutant binding affinity prediction protocol and improvement of the single-mutant success rate. Our results indicate that structure-based computational design can be successfully applied to further improve the binding of high-affinity antibodies. | |||
Affinity enhancement of an in vivo matured therapeutic antibody using structure-based computational design.,Clark LA, Boriack-Sjodin PA, Eldredge J, Fitch C, Friedman B, Hanf KJ, Jarpe M, Liparoto SF, Li Y, Lugovskoy A, Miller S, Rushe M, Sherman W, Simon K, Van Vlijmen H Protein Sci. 2006 May;15(5):949-60. Epub 2006 Apr 5. PMID:16597831<ref>PMID:16597831</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2b2x" style="background-color:#fffaf0;"></div> | |||
== | |||
==See Also== | ==See Also== | ||
*[[ | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[Integrin 3D structures|Integrin 3D structures]] | |||
== | *[[3D structures of non-human antibody|3D structures of non-human antibody]] | ||
< | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Boriack-Sjodin | [[Category: Boriack-Sjodin PA]] | ||
[[Category: Clark | [[Category: Clark LA]] | ||
[[Category: Eldredge | [[Category: Eldredge J]] | ||
[[Category: Fitch | [[Category: Fitch C]] | ||
[[Category: Friedman | [[Category: Friedman B]] | ||
[[Category: Hanf | [[Category: Hanf KJ]] | ||
[[Category: Jarpe | [[Category: Jarpe M]] | ||
[[Category: Li | [[Category: Li Y]] | ||
[[Category: Liparoto | [[Category: Liparoto SF]] | ||
[[Category: Lugovskoy | [[Category: Lugovskoy A]] | ||
Latest revision as of 10:33, 23 August 2023
VLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 FabVLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 Fab
Structural highlights
FunctionITA1_RAT Integrin alpha-1/beta-1 is a receptor for laminin and collagen. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedImproving the affinity of a high-affinity protein-protein interaction is a challenging problem that has practical applications in the development of therapeutic biomolecules. We used a combination of structure-based computational methods to optimize the binding affinity of an antibody fragment to the I-domain of the integrin VLA1. Despite the already high affinity of the antibody (Kd approximately 7 nM) and the moderate resolution (2.8 A) of the starting crystal structure, the affinity was increased by an order of magnitude primarily through a decrease in the dissociation rate. We determined the crystal structure of a high-affinity quadruple mutant complex at 2.2 A. The structure shows that the design makes the predicted contacts. Structural evidence and mutagenesis experiments that probe a hydrogen bond network illustrate the importance of satisfying hydrogen bonding requirements while seeking higher-affinity mutations. The large and diverse set of interface mutations allowed refinement of the mutant binding affinity prediction protocol and improvement of the single-mutant success rate. Our results indicate that structure-based computational design can be successfully applied to further improve the binding of high-affinity antibodies. Affinity enhancement of an in vivo matured therapeutic antibody using structure-based computational design.,Clark LA, Boriack-Sjodin PA, Eldredge J, Fitch C, Friedman B, Hanf KJ, Jarpe M, Liparoto SF, Li Y, Lugovskoy A, Miller S, Rushe M, Sherman W, Simon K, Van Vlijmen H Protein Sci. 2006 May;15(5):949-60. Epub 2006 Apr 5. PMID:16597831[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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