1moe
From Proteopedia
(New page: 200px<br /><applet load="1moe" size="450" color="white" frame="true" align="right" spinBox="true" caption="1moe, resolution 2.6Å" /> '''The three-dimensional...) |
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| - | [[Image:1moe.gif|left|200px]]<br /><applet load="1moe" size=" | + | [[Image:1moe.gif|left|200px]]<br /><applet load="1moe" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1moe, resolution 2.6Å" /> | caption="1moe, resolution 2.6Å" /> | ||
'''The three-dimensional structure of an engineered scFv T84.66 dimer or diabody in VL to VH linkage.'''<br /> | '''The three-dimensional structure of an engineered scFv T84.66 dimer or diabody in VL to VH linkage.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Diabodies (scFv dimers) are small, bivalent antibody mimetics of | + | Diabodies (scFv dimers) are small, bivalent antibody mimetics of approximately 55kDa in size that possess rapid in vivo targeting pharmacokinetics compared to the intact parent antibody, and may prove highly suitable for imaging and therapeutic applications. Here, we describe T84.66Di, the first diabody crystal structure in which the scFvs comprise V domains linked in the V(L)-to-V(H) orientation. The structure was determined by X-ray diffraction analysis to 2.6 A resolution. The T84.66Di scFv was constructed from the anti-carcinoembryonic antigen (anti-CEA) antibody T84.66 variable domains connected by an eight residue peptide linker to provide flexibility between Fv modules and promote dimer formation with bivalent affinity to the cell-surface target, CEA. Therefore, it was surprising to observe a close association of some Fv module complementarity-determining regions in the T84.66 diabody crystal, especially compared to other diabody structures all of which are linked in the opposite V(H)-to-V(L) orientation. The differences between the arrangement of Fv modules in the T84.66Di V(L)-to-V(H) linked diabody structure compared to the crystal structure of L5MK16 and other proposed V(H)-to-V(L) linked diabodies has been investigated and their potential for flexibility discussed. The comparison between V(H)-to-V(L) and V(L)-to-V(H) linked diabodies revealed in this study represents a limited repertoire of possible diabody Fv orientations, but one that reveals the potential flexibility of these molecules. This analysis therefore provides some signposts that may impact on future molecular designs for these therapeutic molecules with respect to diabody flexibility and avidity. |
==About this Structure== | ==About this Structure== | ||
| - | 1MOE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [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:// | + | 1MOE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MOE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Carmichael, J | + | [[Category: Carmichael, J A.]] |
| - | [[Category: Garrett, T | + | [[Category: Garrett, T P.J.]] |
| - | [[Category: Hudson, P | + | [[Category: Hudson, P J.]] |
| - | [[Category: Power, B | + | [[Category: Power, B E.]] |
| - | [[Category: Raubischek, A | + | [[Category: Raubischek, A A.]] |
| - | [[Category: Shively, J | + | [[Category: Shively, J E.]] |
| - | [[Category: Wu, A | + | [[Category: Wu, A M.]] |
| - | [[Category: Yazaki, P | + | [[Category: Yazaki, P J.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: anti carcinoembryonic antigen]] | [[Category: anti carcinoembryonic antigen]] | ||
| Line 26: | Line 26: | ||
[[Category: dimer]] | [[Category: dimer]] | ||
[[Category: scfv]] | [[Category: scfv]] | ||
| - | [[Category: t84 | + | [[Category: t84 66]] |
[[Category: variable domain]] | [[Category: variable domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:57:22 2008'' |
Revision as of 11:57, 21 February 2008
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The three-dimensional structure of an engineered scFv T84.66 dimer or diabody in VL to VH linkage.
Overview
Diabodies (scFv dimers) are small, bivalent antibody mimetics of approximately 55kDa in size that possess rapid in vivo targeting pharmacokinetics compared to the intact parent antibody, and may prove highly suitable for imaging and therapeutic applications. Here, we describe T84.66Di, the first diabody crystal structure in which the scFvs comprise V domains linked in the V(L)-to-V(H) orientation. The structure was determined by X-ray diffraction analysis to 2.6 A resolution. The T84.66Di scFv was constructed from the anti-carcinoembryonic antigen (anti-CEA) antibody T84.66 variable domains connected by an eight residue peptide linker to provide flexibility between Fv modules and promote dimer formation with bivalent affinity to the cell-surface target, CEA. Therefore, it was surprising to observe a close association of some Fv module complementarity-determining regions in the T84.66 diabody crystal, especially compared to other diabody structures all of which are linked in the opposite V(H)-to-V(L) orientation. The differences between the arrangement of Fv modules in the T84.66Di V(L)-to-V(H) linked diabody structure compared to the crystal structure of L5MK16 and other proposed V(H)-to-V(L) linked diabodies has been investigated and their potential for flexibility discussed. The comparison between V(H)-to-V(L) and V(L)-to-V(H) linked diabodies revealed in this study represents a limited repertoire of possible diabody Fv orientations, but one that reveals the potential flexibility of these molecules. This analysis therefore provides some signposts that may impact on future molecular designs for these therapeutic molecules with respect to diabody flexibility and avidity.
About this Structure
1MOE is a Single protein structure of sequence from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
The crystal structure of an anti-CEA scFv diabody assembled from T84.66 scFvs in V(L)-to-V(H) orientation: implications for diabody flexibility., Carmichael JA, Power BE, Garrett TP, Yazaki PJ, Shively JE, Raubischek AA, Wu AM, Hudson PJ, J Mol Biol. 2003 Feb 14;326(2):341-51. PMID:12559905
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