View source for 3qxw


==Free structure of an anti-methotrexate CDR1-4 Graft VHH Antibody==
<StructureSection load='3qxw' size='340' side='right'caption='[[3qxw]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3qxw]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelus_glama Camelus glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QXW FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1i3u|1i3u]], [[2x6m|2x6m]], [[3qxt|3qxt]], [[3qxv|3qxv]], [[3qxu|3qxu]]</div></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=3qxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qxw OCA], [https://pdbe.org/3qxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qxw RCSB], [https://www.ebi.ac.uk/pdbsum/3qxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qxw ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Conventional anti-hapten antibodies typically bind low-molecular weight compounds (haptens) in the crevice between the variable heavy and light chains. Conversely, heavy chain-only camelid antibodies, which lack a light chain, must rely entirely on a single variable domain to recognize haptens. While several anti-hapten VHHs have been generated, little is known regarding the underlying structural and thermodynamic basis for hapten recognition. Here, an anti-methotrexate VHH (anti-MTX VHH) was generated using grafting methods whereby the three complementarity determining regions (CDRs) were inserted onto an existing VHH framework. Thermodynamic analysis of the anti-MTX VHH CDR1-3 Graft revealed a micromolar binding affinity, while the crystal structure of the complex revealed a somewhat surprising noncanonical binding site which involved MTX tunneling under the CDR1 loop. Due to the close proximity of MTX to CDR4, a nonhypervariable loop, the CDR4 loop sequence was subsequently introduced into the CDR1-3 graft, which resulted in a dramatic 1000-fold increase in the binding affinity. Crystal structure analysis of both the free and complex anti-MTX CDR1-4 graft revealed CDR4 plays a significant role in both intermolecular contacts and binding site conformation that appear to contribute toward high affinity binding. Additionally, the anti-MTX VHH possessed relatively high specificity for MTX over closely related compounds aminopterin and folate, demonstrating that VHH domains are capable of binding low-molecular weight ligands with high affinity and specificity, despite their reduced interface.

An anti-hapten camelid antibody reveals a cryptic binding site with significant energetic contributions from a nonhypervariable loop.,Fanning SW, Horn JR Protein Sci. 2011 Jul;20(7):1196-207. doi: 10.1002/pro.648. Epub 2011 May, 23. PMID:21557375<ref>PMID:21557375</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3qxw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Camelus glama]]
[[Category: Large Structures]]
[[Category: Fanning, S W]]
[[Category: Horn, J R]]
[[Category: Anti-hapten antibody]]
[[Category: Antibody]]
[[Category: Camelid single domain antibody]]
[[Category: Cdr]]
[[Category: Hapten binding]]
[[Category: Heavy chain only]]
[[Category: Immune system]]
[[Category: Ligand binding]]
[[Category: Low molecular weight compound]]
[[Category: Methotrexate]]
[[Category: Small molecule sensing]]
[[Category: Vhh]]