2c1p

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[[Image:2c1p.gif|left|200px]]<br /><applet load="2c1p" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2c1p, resolution 2.0&Aring;" />
 
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'''FAB-FRAGMENT OF ENANTIOSELECTIVE ANTIBODY COMPLEXED WITH FINROZOLE'''<br />
 
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==Overview==
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==Fab-fragment of enantioselective antibody complexed with finrozole==
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Enantioselective antibodies can separate the enantiomers of a chiral, compound in a highly specific manner. We have recently reported the, cloning and applications of a recombinant Fab-fragment, ENA11His, in the, enantioseparation of a drug candidate, finrozole, which contains two, chiral centers. Here, the crystal structures of this enantioselective, antibody Fab-fragment are determined in the absence of the hapten at a, resolution of 2.75 A, and in the presence of the hapten at 2.05 A, resolution. The conformation of the protein was found to be similar in, both free and complex forms. The hapten molecule was tightly bound in a, deep cleft between the light and heavy chains of the Fab-fragment. The, complex structure also allowed us to describe the molecular basis for, enantioselectivity and to deduce the absolute configurations of all the, four different stereoisomers (a-d) of finrozole. The ENA11His antibody, fragment selectively binds the SR (a) enantiomer from the racemic mixture, of a and d-enantiomers, thus allowing separation from the, pharmacologically most active RS enantiomer (d). In particular, Asp95 and, Asn35 of the H-chain in the ENA11 His antibody seem to provide this, specificity through hydrogen bonding.
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<StructureSection load='2c1p' size='340' side='right'caption='[[2c1p]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2c1p]] is a 4 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=2C1P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C1P FirstGlance]. <br>
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</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&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FNZ:4-[(1S,2R)-3-(4-FLUOROPHENYL)-2-HYDROXY-1-(1H-1,2,4-TRIAZOL-1-YL)PROPYL]BENZONITRILE'>FNZ</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c1p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c1p OCA], [https://pdbe.org/2c1p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c1p RCSB], [https://www.ebi.ac.uk/pdbsum/2c1p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c1p ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q58EU8_MOUSE Q58EU8_MOUSE]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c1/2c1p_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2c1p ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Enantioselective antibodies can separate the enantiomers of a chiral compound in a highly specific manner. We have recently reported the cloning and applications of a recombinant Fab-fragment, ENA11His, in the enantioseparation of a drug candidate, finrozole, which contains two chiral centers. Here, the crystal structures of this enantioselective antibody Fab-fragment are determined in the absence of the hapten at a resolution of 2.75 A, and in the presence of the hapten at 2.05 A resolution. The conformation of the protein was found to be similar in both free and complex forms. The hapten molecule was tightly bound in a deep cleft between the light and heavy chains of the Fab-fragment. The complex structure also allowed us to describe the molecular basis for enantioselectivity and to deduce the absolute configurations of all the four different stereoisomers (a-d) of finrozole. The ENA11His antibody fragment selectively binds the SR (a) enantiomer from the racemic mixture of a and d-enantiomers, thus allowing separation from the pharmacologically most active RS enantiomer (d). In particular, Asp95 and Asn35 of the H-chain in the ENA11 His antibody seem to provide this specificity through hydrogen bonding.
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==About this Structure==
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Crystal structures of an enantioselective fab-fragment in free and complex forms.,Parkkinen T, Nevanen TK, Koivula A, Rouvinen J J Mol Biol. 2006 Mar 24;357(2):471-80. Epub 2006 Jan 3. PMID:16427081<ref>PMID:16427081</ref>
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2C1P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with FNZ as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Fnz Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2C1P OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal structures of an enantioselective fab-fragment in free and complex forms., Parkkinen T, Nevanen TK, Koivula A, Rouvinen J, J Mol Biol. 2006 Mar 24;357(2):471-80. Epub 2006 Jan 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16427081 16427081]
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</div>
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<div class="pdbe-citations 2c1p" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Koivula A]]
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[[Category: Koivula, A.]]
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[[Category: Nevanen TK]]
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[[Category: Nevanen, T.K.]]
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[[Category: Parkkinen T]]
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[[Category: Parkkinen, T.]]
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[[Category: Rouvinen J]]
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[[Category: Rouvinen, J.]]
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[[Category: FNZ]]
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[[Category: antibody]]
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[[Category: enantioselective]]
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[[Category: enantioselective antibody]]
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[[Category: fab fragment]]
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[[Category: finrozole]]
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[[Category: immune system]]
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[[Category: immunoglobulin domain]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 19:06:10 2007''
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Current revision

Fab-fragment of enantioselective antibody complexed with finrozole

PDB ID 2c1p

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