1ZAN

Crystal structure of anti-NGF AD11 Fab

Summary for 1ZAN

• Entry DOI: 10.2210/pdb1zan/pdb
• Descriptor: Fab AD11 Light Chain, Fab AD11 Heavy Chain, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: immunoglobulin, fab, immune system
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Secreted: P84751
• Total number of polymer chains: 2
• Total formula weight: 46925.48

Authors

Covaceuszach, S.,Cattaneo, A.,Cassetta, A.,Lamba, D. (deposition date: 2005-04-06, release date: 2006-04-04, Last modification date: 2024-10-30)

Primary citation

Covaceuszach, S.,Cassetta, A.,Konarev, P.V.,Gonfloni, S.,Rudolph, R.,Svergun, D.I.,Lamba, D.,Cattaneo, A.
Dissecting NGF interactions with TrkA and p75 receptors by structural and functional studies of an anti-NGF neutralizing antibody.
J.Mol.Biol., 381:881-896, 2008

PubMed Abstract: The anti-nerve growth factor (NGF) monoclonal antibody alphaD11 is a potent antagonist that neutralizes the biological functions of its antigen in vivo. NGF antagonism is expected to be a highly effective and safe therapeutic approach in many pain states. A comprehensive functional and structural analysis of alphaD11 monoclonal antibody was carried out, showing its ability to neutralize NGF binding to either tropomyosine receptor kinase A (TrkA) or p75 receptors. The 3-D structure of the alphaD11 Fab fragment was solved at 1.7 A resolution. A computational docking model of the alphaD11 Fab-NGF complex, based on epitope mapping using a pool of 44 NGF mutants and experimentally validated by small-angle X-ray scattering, provided the structural basis for identifying the residues involved in alphaD11 Fab binding. The present study pinpoints loop II of NGF to be an important structural determinant for NGF biological activity mediated by TrkA receptor.

PubMed: 18635195
DOI: 10.1016/j.jmb.2008.06.008

Experimental method

X-RAY DIFFRACTION (1.7 Å)