1seq
From Proteopedia
(New page: 200px<br /> <applet load="1seq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1seq, resolution 1.78Å" /> '''Fab MNAC13'''<br />...) |
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caption="1seq, resolution 1.78Å" /> | caption="1seq, resolution 1.78Å" /> | ||
'''Fab MNAC13'''<br /> | '''Fab MNAC13'''<br /> | ||
==Overview== | ==Overview== | ||
| - | MNAC13, a mouse monoclonal antibody, recognizes with high affinity and | + | MNAC13, a mouse monoclonal antibody, recognizes with high affinity and specificity the neurotrophin receptor TrkA and displays a neutralizing activity toward the NGF/TrkA interaction. Detailed knowledge of the molecular basis determining the specificity of this antibody is of importance because of its potential use as a modulator of the TrkA-mediated NGF activity. Here, we report a full biochemical and structural characterization of the MNAC13 antibody. Epitope mapping studies, by serial deletion mutants and by phage display, reveal a conformational epitope that is localized on the carboxy-terminal region of the first immunoglobulin-like domain (d4) of TrkA. The X-ray crystal structure of the MNAC13 Fab fragment has been determined and refined to 1.8 A resolution. The antigen-binding site is characterized by a crevice, surrounded by hydrophilic-charged residues on either side, dipping deep toward three mainly hydrophobic subsites. Remarkably an isopropanol molecule has been found to bind in one of the hydrophobic crevices. Overall, the surface topology (shape and electrostatic potential) of the combining site is consistent with the binding data on TrkA ECD serial deletions mutants. The structure of the MNAC13 Fab fragment may assist in the rational structure-based design of high affinity humanized forms of MNAC13, appropriate for therapeutic approaches in neuropathy and inflammatory pain states. |
==About this Structure== | ==About this Structure== | ||
| - | 1SEQ 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 SO4, TRS and IPA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1SEQ 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=SO4:'>SO4</scene>, <scene name='pdbligand=TRS:'>TRS</scene> and <scene name='pdbligand=IPA:'>IPA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SEQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: immunoglobulin]] | [[Category: immunoglobulin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:00:42 2008'' |
Revision as of 13:00, 21 February 2008
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Fab MNAC13
Overview
MNAC13, a mouse monoclonal antibody, recognizes with high affinity and specificity the neurotrophin receptor TrkA and displays a neutralizing activity toward the NGF/TrkA interaction. Detailed knowledge of the molecular basis determining the specificity of this antibody is of importance because of its potential use as a modulator of the TrkA-mediated NGF activity. Here, we report a full biochemical and structural characterization of the MNAC13 antibody. Epitope mapping studies, by serial deletion mutants and by phage display, reveal a conformational epitope that is localized on the carboxy-terminal region of the first immunoglobulin-like domain (d4) of TrkA. The X-ray crystal structure of the MNAC13 Fab fragment has been determined and refined to 1.8 A resolution. The antigen-binding site is characterized by a crevice, surrounded by hydrophilic-charged residues on either side, dipping deep toward three mainly hydrophobic subsites. Remarkably an isopropanol molecule has been found to bind in one of the hydrophobic crevices. Overall, the surface topology (shape and electrostatic potential) of the combining site is consistent with the binding data on TrkA ECD serial deletions mutants. The structure of the MNAC13 Fab fragment may assist in the rational structure-based design of high affinity humanized forms of MNAC13, appropriate for therapeutic approaches in neuropathy and inflammatory pain states.
About this Structure
1SEQ is a Protein complex structure of sequences from Mus musculus with , and as ligands. Full crystallographic information is available from OCA.
Reference
Neutralization of NGF-TrkA receptor interaction by the novel antagonistic anti-TrkA monoclonal antibody MNAC13: a structural insight., Covaceuszach S, Cattaneo A, Lamba D, Proteins. 2005 Feb 15;58(3):717-27. PMID:15625712
Page seeded by OCA on Thu Feb 21 15:00:42 2008
Categories: Mus musculus | Protein complex | Cattaneo, A. | Covaceuszach, S. | Lamba, D. | IPA | SO4 | TRS | Immunoglobulin
