2FGW

X-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

Summary for 2FGW

• Entry DOI: 10.2210/pdb2fgw/pdb
• Descriptor: H52 FAB (LIGHT CHAIN), H52 FAB (HEAVY CHAIN) (2 entities in total)
• Functional Keywords: immunoglobulin, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 48449.98

Authors

Eigenbrot, C.,Kessler, J. (deposition date: 1994-01-16, release date: 1994-04-30, Last modification date: 2024-11-20)

Primary citation

Eigenbrot, C.,Gonzalez, T.,Mayeda, J.,Carter, P.,Werther, W.,Hotaling, T.,Fox, J.,Kessler, J.
X-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.
Proteins, 18:49-62, 1994

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.

PubMed: 7908437
DOI: 10.1002/prot.340180107

Experimental method

X-RAY DIFFRACTION (3 Å)