1i9j
From Proteopedia
(New page: 200px<br /><applet load="1i9j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i9j, resolution 2.60Å" /> '''TESTOSTERONE COMPLEX...) |
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| - | [[Image:1i9j.gif|left|200px]]<br /><applet load="1i9j" size=" | + | [[Image:1i9j.gif|left|200px]]<br /><applet load="1i9j" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1i9j, resolution 2.60Å" /> | caption="1i9j, resolution 2.60Å" /> | ||
'''TESTOSTERONE COMPLEX STRUCTURE OF THE RECOMBINANT MONOCLONAL WILD TYPE ANTI-TESTOSTERONE FAB FRAGMENT'''<br /> | '''TESTOSTERONE COMPLEX STRUCTURE OF THE RECOMBINANT MONOCLONAL WILD TYPE ANTI-TESTOSTERONE FAB FRAGMENT'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The monoclonal anti-testosterone antibody (3-C(4)F(5)) has a relatively | + | The monoclonal anti-testosterone antibody (3-C(4)F(5)) has a relatively high affinity (3 x 10(8) m(-1)) with an overall good specificity profile. However, the earlier characterized binding properties have shown that both the affinity and specificity of this antibody must be improved if it is intended for use in clinical immunoassays. In this paper, the crystal structures of the recombinant anti-testosterone (3-C(4)F(5)) Fab fragment have been determined in the testosterone-bound and free form at resolutions of 2.60 and 2.72 A, respectively. The high affinity binding of the (3-C(4)F(5)) Fab is mainly determined by shape complementarity between the protein and testosterone. Only one direct hydrogen bond is formed between the hydroxyl group of the testosterone D-ring and the main-chain oxygen of Gly100(J)H. The testosterone is deeply bound in a hydrophobic pocket, and the close shape complementarity is mainly formed by the third complementarity-determining regions (CDR) of the heavy and light chain. Comparison of the bound structure with the free structure indicates conformational changes in the protein upon testosterone binding. The conformational changes of the side chains of two residues Glu95H and Tyr99H in the CDR-H3 are particularly essential for the binding. Interesting similarities in the binding of different steroids were also observed upon comparison of the available structures of anti-steroid antibodies. |
==About this Structure== | ==About this Structure== | ||
| - | 1I9J 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 TES as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1I9J 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=TES:'>TES</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I9J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: testosterone]] | [[Category: testosterone]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:09:27 2008'' |
Revision as of 11:09, 21 February 2008
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TESTOSTERONE COMPLEX STRUCTURE OF THE RECOMBINANT MONOCLONAL WILD TYPE ANTI-TESTOSTERONE FAB FRAGMENT
Overview
The monoclonal anti-testosterone antibody (3-C(4)F(5)) has a relatively high affinity (3 x 10(8) m(-1)) with an overall good specificity profile. However, the earlier characterized binding properties have shown that both the affinity and specificity of this antibody must be improved if it is intended for use in clinical immunoassays. In this paper, the crystal structures of the recombinant anti-testosterone (3-C(4)F(5)) Fab fragment have been determined in the testosterone-bound and free form at resolutions of 2.60 and 2.72 A, respectively. The high affinity binding of the (3-C(4)F(5)) Fab is mainly determined by shape complementarity between the protein and testosterone. Only one direct hydrogen bond is formed between the hydroxyl group of the testosterone D-ring and the main-chain oxygen of Gly100(J)H. The testosterone is deeply bound in a hydrophobic pocket, and the close shape complementarity is mainly formed by the third complementarity-determining regions (CDR) of the heavy and light chain. Comparison of the bound structure with the free structure indicates conformational changes in the protein upon testosterone binding. The conformational changes of the side chains of two residues Glu95H and Tyr99H in the CDR-H3 are particularly essential for the binding. Interesting similarities in the binding of different steroids were also observed upon comparison of the available structures of anti-steroid antibodies.
About this Structure
1I9J is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
Structural insights into steroid hormone binding: the crystal structure of a recombinant anti-testosterone Fab fragment in free and testosterone-bound forms., Valjakka J, Takkinenz K, Teerinen T, Soderlund H, Rouvinen J, J Biol Chem. 2002 Feb 8;277(6):4183-90. Epub 2001 Nov 13. PMID:11707437
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