1h8n

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(New page: 200px<br /> <applet load="1h8n" size="450" color="white" frame="true" align="right" spinBox="true" caption="1h8n, resolution 1.87&Aring;" /> '''THREE-DIMENSIONAL S...)
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[[Image:1h8n.gif|left|200px]]<br />
 
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<applet load="1h8n" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1h8n, resolution 1.87&Aring;" />
 
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'''THREE-DIMENSIONAL STRUCTURE OF ANTI-AMPICILLIN SINGLE CHAIN FV FRAGMENT FROM PHAGE-DISPLAYED MURINE ANTIBODY LIBRARIES'''<br />
 
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==Overview==
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==Three-dimensional structure of anti-ampicillin single chain Fv fragment from phage-displayed murine antibody libraries==
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The N-terminal segment (FR-H1) of the heavy chain (V(H)) of antibodies, shows significant conformational variability correlating with the nature, of the amino acids H6, H7 and H10 (Kabat H9). In this study, we have, established a causal relationship between the local sequence and the, structure of this framework region and linked this relationship to, important biophysical properties such as affinity, folding yield and, stability. We have generated six mutants of the scFv fragment aL2, covering some of the most abundant amino acid combinations in positions, H6, H7 and H10 (according to a new consensus nomenclature, Kabat H9). For, the aL2 wild-type (w.t.) with the sequence 6(Q)7(P)10(A) and for two of, the mutants, the X-ray structures have been determined. The structure of, the triple mutant aL2-6(E)7(S)10(G) shows the FR-H1 backbone conformations, predicted for this amino acid combination, which is distinctly different, from the structure of the w.t, thus supporting our hypothesis that these, residues determine the conformation of this segment. The mutant, aL2-6(E)7(P)10(G) represents a residue combination not occurring in, natural antibody sequences. It shows a completely different, unique, structure in the first beta-strand of V(H), not observed in natural Fv, fragments and forms a novel type of diabody. Two V(H) domains of the, mutant associate by swapping the first beta-strand., Concentration-dependent changes in Trp fluorescence indicate that this, dimerization also occurs in solution. The mutations in amino acids H6, H7, and H10 (Kabat H9) influence the dimerization behavior of the scFv and its, thermodynamic stability. All the observations reported here have practical, implications for the cloning of Fv fragments with degenerate primers, as, well as for the design of new antibodies by CDR grafting or synthetic, libraries.
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<StructureSection load='1h8n' size='340' side='right'caption='[[1h8n]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1h8n]] is a 1 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=1H8N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H8N 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]] 1.87&#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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1h8n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h8n OCA], [https://pdbe.org/1h8n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h8n RCSB], [https://www.ebi.ac.uk/pdbsum/1h8n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h8n ProSAT]</span></td></tr>
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</table>
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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/h8/1h8n_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=1h8n ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1H8N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mouse_e_010090 Mouse e 010090] with SO4 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H8N OCA].
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*[[Antibody 3D structures|Antibody 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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The importance of framework residues H6, H7 and H10 in antibody heavy chains: experimental evidence for a new structural subclassification of antibody V(H) domains., Jung S, Spinelli S, Schimmele B, Honegger A, Pugliese L, Cambillau C, Pluckthun A, J Mol Biol. 2001 Jun 8;309(3):701-16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11397090 11397090]
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[[Category: Large Structures]]
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[[Category: Mouse e 010090]]
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[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Cambillau C]]
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[[Category: Cambillau, C.]]
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[[Category: Honegger A]]
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[[Category: Honegger, A.]]
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[[Category: Jung S]]
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[[Category: Jung, S.]]
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[[Category: Pluckthun A]]
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[[Category: Pluckthun, A.]]
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[[Category: Pugliese L]]
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[[Category: Pugliese, L.]]
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[[Category: Schimmele B]]
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[[Category: Schimmele, B.]]
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[[Category: Spinelli S]]
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[[Category: Spinelli, S.]]
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[[Category: GOL]]
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[[Category: SO4]]
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[[Category: antibody]]
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[[Category: framework]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:31:30 2007''
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Current revision

Three-dimensional structure of anti-ampicillin single chain Fv fragment from phage-displayed murine antibody libraries

PDB ID 1h8n

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