Download MendeleyX-ray structures of fragments from binding and nonbinding versions of a humanized anti-CD18 antibody: structural indications of the key role of VH residues 59 to 65.
Eigenbrot, C., Gonzalez, T., Mayeda, J., Carter, P., Werther, W., Hotaling, T., Fox, J., Kessler, J.(1994) Proteins 18: 49-62
- PubMed: 7908437
- DOI: https://doi.org/10.1002/prot.340180107
- Primary Citation of Related Structures:
1FGV, 2FGW - PubMed Abstract:
X-ray crystal structures of fragments from two different humanized anti-CD18 antibodies are reported. The Fv fragment of the nonbinding version has been refined in space group C2 with a = 64.2 A, b = 61.3 A, c = 51.8 A, and beta = 99 degrees to an R-value of 18.0% at 1.9 A, and the Fab fragment of the tight-binding version has been refined in space group P3 with a = 101. A and c = 45.5 A to an R-value of 17.8% at 3.0 A resolution. The very large difference in their binding affinity (> 1000-fold) is attributed to large and local structural differences in the C-terminal part of CDR-H2, and from this we conclude there is direct contact between this region and antigen when they combine. X-ray structures of antibody-antigen complexes available in the literature have yet to show this part of CDR-H2 in contact with antigen, despite its hypervariable sequence. Implications of this result for antibody humanization are discussed.
Organizational Affiliation:
Department of Protein Engineering, Genentech, Inc., South San Francisco, California 94080-4990.
