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1fl5

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(New page: 200px<br /> <applet load="1fl5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fl5, resolution 2.10&Aring;" /> '''THE UNLIGANDED GERM...)
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[[Image:1fl5.gif|left|200px]]<br />
 
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<applet load="1fl5" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1fl5, resolution 2.10&Aring;" />
 
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'''THE UNLIGANDED GERMLINE PRECURSOR TO THE SULFIDE OXIDASE CATALYTIC ANTIBODY 28B4.'''<br />
 
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==Overview==
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==THE UNLIGANDED GERMLINE PRECURSOR TO THE SULFIDE OXIDASE CATALYTIC ANTIBODY 28B4.==
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In an effort to gain greater insight into the evolution of the redox, active, catalytic antibody 28B4, the germline genes used by the mouse to, generate this antibody were cloned and expressed, and the X-ray crystal, structures of the unliganded and hapten-bound germline Fab of antibody, 28B4 were determined. Comparison with the previously determined structures, of the unliganded and hapten-bound affinity-matured Fab [Hsieh-Wilson, L., C., Schultz, P. G., and Stevens, R. C. (1996) Proc. Natl. Acad. Sci., U.S.A. 93, 5363] shows that the germline antibody binds the p-nitrophenyl, ring of hapten 3 in an orientation significantly different from that seen, in the affinity-matured antibody, whereas the phosphonate moiety is bound, in a similar mode by both antibodies. The affinity-matured antibody 28B4, has more electrostatic and hydrophobic interactions with hapten 3 than the, germline antibody and binds the hapten in a lock-and-key fashion. In, contrast, significant conformational changes occur in the loops of CDR H3, and CDR L1 upon hapten binding to the germline antibody, consistent with, the notion of structural plasticity in the germline antibody-combining, site [Wedemayer, G. J., Patten, P. A., Wang, L. H., Schultz, P. G., and, Stevens, R. C. (1997) Science 276, 1665]. The structural differences are, reflected in the differential binding affinities of the germline Fab (K(d), = 25 microM) and 28B4 Fab (K(d) = 37 nM) to hapten 3. Nine replacement, mutations were found to accumulate in the affinity-matured antibody 28B4, compared to its germline precursor. The effects of each mutation on the, binding affinity of the antibody to hapten 3 were characterized in detail, in the contexts of both the germline and the affinity-matured antibodies., One of the mutations, Asp95(H)Trp, leads to a change in the orientation of, the bound hapten, and its presence is a prerequisite for other somatic, mutations to enhance the binding affinity of the germline antibody for, hapten 3. Thus, the germline antibody of 28B4 acquired functionally, important mutations in a stepwise manner, which fits into a multicycle, mutation, affinity selection, and clonal expansion model for germline, antibody evolution. Two other antibodies, 20-1 and NZA6, with very, different antigen specificities were found to be highly homologous to the, germline antibody of 28B4, consistent with the notion that certain, germline variable-region gene combinations can give rise to polyspecific, hapten binding sites [Romesberg, F. E., Spiller, B., Schultz, P. G., and, Stevens, R. C. (1998) Science 279, 1929]. The ultimate specificity of the, polyspecific germline antibody appears to be defined by CDR H3 variability, and subsequent somatic mutation. Insights into the evolution of, antibody-combining sites provided by this and other structural studies are, discussed.
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<StructureSection load='1fl5' size='340' side='right'caption='[[1fl5]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1fl5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FL5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FL5 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]] 2.1&#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=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=1fl5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fl5 OCA], [https://pdbe.org/1fl5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fl5 RCSB], [https://www.ebi.ac.uk/pdbsum/1fl5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fl5 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/fl/1fl5_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=1fl5 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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1FL5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FL5 OCA].
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*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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A comparative analysis of the immunological evolution of antibody 28B4., Yin J, Mundorff EC, Yang PL, Wendt KU, Hanway D, Stevens RC, Schultz PG, Biochemistry. 2001 Sep 11;40(36):10764-73. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11535051 11535051]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Protein complex]]
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[[Category: Hanway D]]
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[[Category: Hanway, D.]]
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[[Category: Mundorff EC]]
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[[Category: Mundorff, E.C.]]
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[[Category: Schultz PG]]
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[[Category: Schultz, P.G.]]
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[[Category: Stevens RC]]
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[[Category: Stevens, R.C.]]
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[[Category: Wendt KU]]
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[[Category: Wendt, K.U.]]
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[[Category: Yang PL]]
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[[Category: Yang, P.L.]]
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[[Category: Yin J]]
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[[Category: Yin, J.]]
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[[Category: SO4]]
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[[Category: catalytic antibody]]
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[[Category: germline antibody]]
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[[Category: sulfide oxidase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:30:24 2007''
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Current revision

THE UNLIGANDED GERMLINE PRECURSOR TO THE SULFIDE OXIDASE CATALYTIC ANTIBODY 28B4.

PDB ID 1fl5

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