1zan

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Crystal structure of anti-NGF AD11 Fab

Structural highlights

1zan is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.7Å
Ligands:CL
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q4KM66_RAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Dissecting NGF interactions with TrkA and p75 receptors by structural and functional studies of an anti-NGF neutralizing antibody.,Covaceuszach S, Cassetta A, Konarev PV, Gonfloni S, Rudolph R, Svergun DI, Lamba D, Cattaneo A J Mol Biol. 2008 Sep 12;381(4):881-96. Epub 2008 Jun 10. PMID:18635195[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. Covaceuszach S, Cassetta A, Konarev PV, Gonfloni S, Rudolph R, Svergun DI, 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. 2008 Sep 12;381(4):881-96. Epub 2008 Jun 10. PMID:18635195 doi:http://dx.doi.org/10.1016/j.jmb.2008.06.008

Contents


PDB ID 1zan

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