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| | <StructureSection load='1l7t' size='340' side='right'caption='[[1l7t]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='1l7t' size='340' side='right'caption='[[1l7t]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1l7t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L7T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L7T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1l7t]] is a 2 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=1L7T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L7T FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1l7s|1l7s]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l7t OCA], [http://pdbe.org/1l7t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l7t RCSB], [http://www.ebi.ac.uk/pdbsum/1l7t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1l7t ProSAT]</span></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=1l7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l7t OCA], [https://pdbe.org/1l7t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l7t RCSB], [https://www.ebi.ac.uk/pdbsum/1l7t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l7t ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q65ZC0_MOUSE Q65ZC0_MOUSE] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l7/1l7t_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l7/1l7t_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Hemminki, A]] | + | [[Category: Hemminki A]] |
| - | [[Category: Niemi, S]] | + | [[Category: Niemi S]] |
| - | [[Category: Rouvinen, J]] | + | [[Category: Rouvinen J]] |
| - | [[Category: Soderlund, H]] | + | [[Category: Soderlund H]] |
| - | [[Category: Takkinen, K]] | + | [[Category: Takkinen K]] |
| - | [[Category: Valjakka, J]] | + | [[Category: Valjakka J]] |
| - | [[Category: Affinity and specificity matured]]
| + | |
| - | [[Category: Anti-testosterone]]
| + | |
| - | [[Category: Fab fragment]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Function
Q65ZC0_MOUSE
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
A highly selective, high affinity recombinant anti-testosterone Fab fragment has been generated by stepwise optimization of the complementarity-determining regions (CDRs) by random mutagenesis and phage display selection of a monoclonal antibody (3-C(4)F(5)). The best mutant (77 Fab) was obtained by evaluating the additivity effects of different independently selected CDR mutations. The 77 Fab contains 20 mutations and has about 40-fold increased affinity (K(d) = 3 x 10(-10) m) when compared with the wild-type (3-C(4)F(5)) Fab. To obtain structural insight into factors, which are needed to improve binding properties, we have determined the crystal structures of the mutant 77 Fab fragment with (2.15 A) and without testosterone (2.10 A) and compared these with previously determined wild-type structures. The overall testosterone binding of the 77 Fab is similar to that of the wild-type. The improved affinity and specificity of the 77 Fab fragment are due to more comprehensive packing of the testosterone with the protein, which is the result of small structural changes within the variable domains. Only one important binding site residue Glu-95 of the heavy chain CDR3 is mutated to alanine in the 77 Fab fragment. This mutation, originally selected from the phage library based on improved specificity, provides more free space for the testosterone D-ring. The light chain CDR1 of 77 Fab containing eight mutations has the most significant effect on the improved affinity, although it has no direct contact with the testosterone. The mutations of CDR-L1 cause a rearrangement in its conformation, leading to an overall fine reshaping of the binding site.
Crystal structure of an in vitro affinity- and specificity-matured anti-testosterone Fab in complex with testosterone. Improved affinity results from small structural changes within the variable domains.,Valjakka J, Hemminki A, Niemi S, Soderlund H, Takkinen K, Rouvinen J J Biol Chem. 2002 Nov 15;277(46):44021-7. Epub 2002 Aug 23. PMID:12196551[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Valjakka J, Hemminki A, Niemi S, Soderlund H, Takkinen K, Rouvinen J. Crystal structure of an in vitro affinity- and specificity-matured anti-testosterone Fab in complex with testosterone. Improved affinity results from small structural changes within the variable domains. J Biol Chem. 2002 Nov 15;277(46):44021-7. Epub 2002 Aug 23. PMID:12196551 doi:10.1074/jbc.M208392200
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