1e4w
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /> <applet load="1e4w" size="450" color="white" frame="true" align="right" spinBox="true" caption="1e4w, resolution 1.95Å" /> '''CROSSREACTIVE BINDI...)
Next diff →
Revision as of 07:22, 18 November 2007
|
CROSSREACTIVE BINDING OF A CIRCULARIZED PEPTIDE TO AN ANTI-TGFALPHA ANTIBODY FAB-FRAGMENT
Overview
The monoclonal antibody tAb2 binds the N-terminal sequence of transforming, growth factor alpha, VVSHFND. With the help of combinatorial peptide, libraries it is possible to find homologous peptides that bind tAb2 with, an affinity similar to that of the epitope. The conformational flexibility, of short peptides can be constrained by cyclization in order to improve, their affinity to the antibody and their stability towards proteolysis., Two cyclic peptides which are cross-reactive binders for tAb2 were, selected earlier using combinatorial peptide libraries. One is cyclized by, an amide bond between the N-alpha group and the side-chain of the last, residue (cyclo-SHFNEYE), and the other by a disulfide bridge, (cyclo-CSHFNDYC). The complex structures of tAb2 with the linear epitope, peptide VVSHFND and with cyclo-SHFNEYE were determined by X-ray, diffraction. Both peptides show a similar conformation and binding pattern, in the complex. The linear peptide SHFNEYE does not bind tAb2, but, cyclo-SHFNEYE is stabilized in a loop conformation suitable for binding., Hence the cyclization counteracts the exchange of aspartate in the epitope, sequence to glutamate. Isothermal titration calorimetry was used to, characterize the binding energetics of tAb2 with the two cyclic peptides, and the epitope peptide. The binding reactions are enthalpically driven, with an unfavorable entropic contribution under all measured conditions., The association reactions are characterized by negative DeltaC(p) changes, and by the uptake of one proton per binding site. A putative candidate for, proton uptake during binding is the histidine residue in each of the, peptides. Hydrogen bonds and the putative formation of an electrostatic, pair between the protonated histidine and a carboxy group may contribute, markedly to the favorable enthalpy of complex formation.Implications to, cyclization of peptides for stabilization are discussed.
About this Structure
1E4W is a Single protein structure of sequence from Mus musculus with NI and CL as ligands. Full crystallographic information is available from OCA.
Reference
Cross-reactive binding of cyclic peptides to an anti-TGFalpha antibody Fab fragment: an X-ray structural and thermodynamic analysis., Hahn M, Winkler D, Welfle K, Misselwitz R, Welfle H, Wessner H, Zahn G, Scholz C, Seifert M, Harkins R, Schneider-Mergener J, Hohne W, J Mol Biol. 2001 Nov 23;314(2):293-309. PMID:11718562
Page seeded by OCA on Sun Nov 18 09:29:01 2007
