3qxu: Difference between revisions

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-[[Image:3qxu.jpg|left|200px]]
-<!--
+==Free Structure of an Anti-Methotrexate CDR1-3 Graft VHH Antibody==
-The line below this paragraph, containing "STRUCTURE_3qxu", creates the "Structure Box" on the page.
+<StructureSection load='3qxu' size='340' side='right'caption='[[3qxu]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3qxu]] is a 4 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=3QXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QXU FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>
-{{STRUCTURE_3qxu|  PDB=3qxu  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qxu OCA], [https://pdbe.org/3qxu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qxu RCSB], [https://www.ebi.ac.uk/pdbsum/3qxu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qxu 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.
-===Free Structure of an Anti-Methotrexate CDR1-3 Graft VHH Antibody===
+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 3qxu" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_21557375}}, adds the Publication Abstract to the page
+*[[Antibody 3D structures|Antibody 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 21557375 is the PubMed ID number.
+*[[3D structures of non-human antibody|3D structures of non-human antibody]]
--->
+== References ==
-{{ABSTRACT_PUBMED_21557375}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-[[3qxu]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QXU OCA].
-==Reference==
-<ref group="xtra">PMID:021557375</ref><references group="xtra"/>
 [[Category: Lama glama]]
-[[Category: Fanning, S W.]]
+[[Category: Large Structures]]
-[[Category: Horn, J R.]]
+[[Category: Fanning SW]]
-[[Category: Anti-hapten antibody]]
+[[Category: Horn JR]]
-[[Category: Antibody]]
-[[Category: Camelid single domain antibody]]
-[[Category: Cdr]]
-[[Category: Cdr1]]
-[[Category: Cdr4]]
-[[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]]