Characterization of crystals of an antibody-recognition fragment of the cancer differentiation antigen mesothelin in complex with the therapeutic antibody MORAb-009

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Aug 1;68(Pt 8):950-3. doi: 10.1107/S1744309112028229. Epub 2012 Jul 31.

Abstract

The mesothelin-specific monoclonal antibody MORAb-009 is capable of blocking the binding of mesothelin to CA-125 and displays promising anticancer potential. It is currently undergoing clinical trials. In order to understand the basis of the interaction between MORAb-009 and mesothelin at atomic resolution, both the Fab fragment of MORAb-009 and the complex between the Fab and an N-terminal fragment of mesothelin (residues 7-64) were crystallized. The crystals of the Fab diffracted X-rays to 1.75 Å resolution and had the symmetry of space group P4(1)2(1)2, with unit-cell parameters a = b = 140.6, c = 282.0 Å. The crystals of the mesothelin-Fab complex diffracted to 2.6 Å resolution and belonged to the hexagonal space group P6(4), with unit-cell parameters a = b = 146.2, c = 80.9 Å. Structural analyses of these molecules are in progress.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antigen-Antibody Complex / chemistry*
  • Antigen-Antibody Complex / immunology
  • Crystallization
  • GPI-Linked Proteins / chemistry*
  • GPI-Linked Proteins / immunology
  • Immunoglobulin Fab Fragments / chemistry*
  • Immunoglobulin Fab Fragments / immunology
  • Mesothelin

Substances

  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • GPI-Linked Proteins
  • Immunoglobulin Fab Fragments
  • amatuximab
  • Mesothelin