View source for 6nfn


==Fab fragment of anti-cocaine antibody h2E2 bound to benzoylecgonine==
<StructureSection load='6nfn' size='340' side='right'caption='[[6nfn]], [[Resolution|resolution]] 2.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nfn]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NFN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NFN 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]] 2.63&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BCG:3-(BENZOYLOXY)-8-METHYL-8-AZABICYCLO[3.2.1]OCTANE-2-CARBOXYLIC+ACID'>BCG</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6nfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nfn OCA], [https://pdbe.org/6nfn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nfn RCSB], [https://www.ebi.ac.uk/pdbsum/6nfn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nfn ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
A high-affinity anti-cocaine monoclonal antibody, designated h2E2, is entering phase 1 clinical trials for cocaine abuse therapy. To gain insight into the molecular details of its structure that are important for binding cocaine and cocaine metabolites, the Fab fragment was generated and crystallized with and without ligand. Structures of the unliganded Fab and the Fab fragment bound to benzoylecgonine were determined, and were compared with each other and with other crystallized anti-cocaine antibodies. The affinity of the h2E2 antibody for cocaine is 4 nM, while that of the cocaine metabolite benzoylecgonine is 20 nM. Both are higher than the reported affinity for cocaine of the two previously crystallized anti-cocaine antibodies. Consistent with cocaine fluorescent quenching binding studies for the h2E2 mAb, four aromatic residues in the CDR regions of the Fab (TyrL32, TyrL96, TrpL91 and TrpH33) were found to be involved in ligand binding. The aromatic side chains surround and trap the tropane moiety of the ligand in the complex structure, forming significant van der Waals interactions which may account for the higher affinity observed for the h2E2 antibody. A water molecule mediates hydrogen bonding between the antibody and the carbonyl group of the benzoyl ester. The affinity of binding to h2E2 of benzoylecgonine differs only by a factor of five compared with that of cocaine; therefore, it is suggested that h2E2 would bind cocaine in the same way as observed in the Fab-benzoylecgonine complex, with minor rearrangements of some hypervariable segments of the antibody.

Structural analysis of free and liganded forms of the Fab fragment of a high-affinity anti-cocaine antibody, h2E2.,Tan K, Zhou M, Ahrendt AJ, Duke NEC, Tabaja N, Ball WJ, Kirley TL, Norman AB, Joachimiak A, Schiffer M, Wilton R, Pokkuluri PR Acta Crystallogr F Struct Biol Commun. 2019 Nov 1;75(Pt 11):697-706. doi:, 10.1107/S2053230X19013608. Epub 2019 Nov 5. PMID:31702583<ref>PMID:31702583</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6nfn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Pokkuluri PR]]
[[Category: Tan K]]