1jnn
From Proteopedia
(New page: 200px<br /> <applet load="1jnn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jnn, resolution 3.2Å" /> '''Crystal Structure of...) |
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| - | [[Image:1jnn.gif|left|200px]]<br /> | + | [[Image:1jnn.gif|left|200px]]<br /><applet load="1jnn" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1jnn" size=" | + | |
caption="1jnn, resolution 3.2Å" /> | caption="1jnn, resolution 3.2Å" /> | ||
'''Crystal Structure of Fab-Estradiol Complexes'''<br /> | '''Crystal Structure of Fab-Estradiol Complexes'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Subtle modulation of antibody-binding properties by protein engineering | + | Subtle modulation of antibody-binding properties by protein engineering often lies with an accurate structural and energetic description of how an antigen is recognised. Thus, with the intent to increase the affinity and add a bias in favour of natural estradiol compared with its chemically modified immunogen, we have determined the crystal structure of two anti-estradiol monoclonal antibodies, 10G6D6 and 17E12E5. Although generated against the same estradiol derivative, these antibodies share little sequence identity, which is reflected in dissimilar binding pockets and in different positioning of the steroid. In both antibodies the characteristic 17-hydroxyl group is buried deeply at the bottom of hydrophobic pockets and stabilised by hydrogen bonds. Apart from this similarity, the steroid is oriented differently in the respective binding pockets. The high specificity of both antibodies has been mapped out, and even closely related steroids show low cross-reactivity. The structural studies of the complex formed between 10G6D6 and 6-CMO-estradiol have identified contacts between the 6-CMO coupling linker and an arginine residue from the heavy chain CDR2 segment. This segment is now being targeted by random mutagenesis to select mutants with a preference for natural estradiol compared to the branched hapten. |
==About this Structure== | ==About this Structure== | ||
| - | 1JNN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with EST as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1JNN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=EST:'>EST</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JNN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Battail-Poirot, N.]] | [[Category: Battail-Poirot, N.]] | ||
[[Category: Bettsworth, F.]] | [[Category: Bettsworth, F.]] | ||
| - | [[Category: Charbonnier, J | + | [[Category: Charbonnier, J B.]] |
[[Category: Derrien, L.]] | [[Category: Derrien, L.]] | ||
| - | [[Category: Du, M | + | [[Category: Du, M H.Le.]] |
[[Category: Ducancel, F.]] | [[Category: Ducancel, F.]] | ||
[[Category: Gilquin, B.]] | [[Category: Gilquin, B.]] | ||
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[[Category: Monnet, C.]] | [[Category: Monnet, C.]] | ||
[[Category: Sibai, G.]] | [[Category: Sibai, G.]] | ||
| - | [[Category: Stura, E | + | [[Category: Stura, E A.]] |
[[Category: Zinn-Justin, S.]] | [[Category: Zinn-Justin, S.]] | ||
[[Category: EST]] | [[Category: EST]] | ||
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[[Category: igg fold]] | [[Category: igg fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:24:43 2008'' |
Revision as of 11:24, 21 February 2008
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Crystal Structure of Fab-Estradiol Complexes
Overview
Subtle modulation of antibody-binding properties by protein engineering often lies with an accurate structural and energetic description of how an antigen is recognised. Thus, with the intent to increase the affinity and add a bias in favour of natural estradiol compared with its chemically modified immunogen, we have determined the crystal structure of two anti-estradiol monoclonal antibodies, 10G6D6 and 17E12E5. Although generated against the same estradiol derivative, these antibodies share little sequence identity, which is reflected in dissimilar binding pockets and in different positioning of the steroid. In both antibodies the characteristic 17-hydroxyl group is buried deeply at the bottom of hydrophobic pockets and stabilised by hydrogen bonds. Apart from this similarity, the steroid is oriented differently in the respective binding pockets. The high specificity of both antibodies has been mapped out, and even closely related steroids show low cross-reactivity. The structural studies of the complex formed between 10G6D6 and 6-CMO-estradiol have identified contacts between the 6-CMO coupling linker and an arginine residue from the heavy chain CDR2 segment. This segment is now being targeted by random mutagenesis to select mutants with a preference for natural estradiol compared to the branched hapten.
About this Structure
1JNN is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
Highly specific anti-estradiol antibodies: structural characterisation and binding diversity., Monnet C, Bettsworth F, Stura EA, Le Du MH, Menez R, Derrien L, Zinn-Justin S, Gilquin B, Sibai G, Battail-Poirot N, Jolivet M, Menez A, Arnaud M, Ducancel F, Charbonnier JB, J Mol Biol. 2002 Jan 25;315(4):699-712. PMID:11812141
Page seeded by OCA on Thu Feb 21 13:24:43 2008
Categories: Mus musculus | Protein complex | Arnaud, M. | Battail-Poirot, N. | Bettsworth, F. | Charbonnier, J B. | Derrien, L. | Du, M H.Le. | Ducancel, F. | Gilquin, B. | Jolivet, M. | Menez, A. | Menez, R. | Monnet, C. | Sibai, G. | Stura, E A. | Zinn-Justin, S. | EST | Antibody-hapten complex | Estradiol | Igg fold
