8FAB

CRYSTAL STRUCTURE OF THE FAB FRAGMENT FROM THE HUMAN MYELOMA IMMUNOGLOBULIN IGG HIL AT 1.8 ANGSTROMS RESOLUTION

Summary for 8FAB

• Entry DOI: 10.2210/pdb8fab/pdb
• Descriptor: IGG1-LAMBDA HIL FAB (LIGHT CHAIN), IGG1-LAMBDA HIL FAB (HEAVY CHAIN) (3 entities in total)
• Functional Keywords: immunoglobulin
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 93714.83

Authors

Saul, F.A.,Poljak, R.J. (deposition date: 1992-03-23, release date: 1993-10-31, Last modification date: 2024-11-20)

Primary citation

Strong, R.K.,Campbell, R.,Rose, D.R.,Petsko, G.A.,Sharon, J.,Margolies, M.N.
Three-dimensional structure of murine anti-p-azophenylarsonate Fab 36-71. 1. X-ray crystallography, site-directed mutagenesis, and modeling of the complex with hapten.
Biochemistry, 30:3739-3748, 1991

PubMed Abstract: The structure of the antigen-binding fragment (Fab) of an anti-p-azophenylarsonate monoclonal antibody, 36-71, bearing a major cross-reactive idiotype of A/J mice has been refined to an R factor of 24.8% at a resolution of 1.85 A. The previously solved partial structure of this Fab at a resolution of 2.9 A (Rose et al., 1990) was used as an initial model for refinement against the high-resolution data. The complex with hapten has been modeled by docking the small-molecule crystal structure of phenylarsonic acid into the structure of the native Fab on the basis of a low-resolution electron density map of the complex. In this model, residue Arg-96 in the light chain and residues Asn-35, Trp-47, and Ser-99 in the heavy chain contact the arsonate moiety of the hapten; an additional bond is found between the arsonate group and a tightly bound water molecule. The phenyl moiety of the hapten packs against two tyrosine side chains at positions 50 and 106 in the heavy chain. Residue Arg-96 in the light chain had been implicated as involved in hapten binding on the basis of previous experiments, and indeed, this residue appears to play a crucial role in this model. Experiments employing site-directed mutagenesis directly support this conclusion. The heavy-chain complementarity-determining regions have novel conformations not previously observed in immunoglobulins except for the recently solved anti-p-azophenylarsonate Fab R 19.9 (Lascombe et al., 1989).

PubMed: 2015229
DOI: 10.1021/bi00229a022

Experimental method

X-RAY DIFFRACTION (1.8 Å)