1QOK

MFE-23 AN ANTI-CARCINOEMBRYONIC ANTIGEN SINGLE-CHAIN FV ANTIBODY

1QOK の概要

• エントリーDOI: 10.2210/pdb1qok/pdb
• 分子名称: MFE-23 RECOMBINANT ANTIBODY FRAGMENT (2 entities in total)
• 機能のキーワード: immunoglobulin, single-chain fv, anti-carcinoembryonic antigen
• 由来する生物種: MUS MUSCULUS (MOUSE)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29874.99

構造登録者

Boehm, M.K.,Corper, A.L.,Wan, T.,Sohi, M.K.,Sutton, B.J.,Thornton, J.D.,Keep, P.A.,Chester, K.A.,Begent, R.H.J.,Perkins, S.J. (登録日: 1999-11-11, 公開日: 2000-11-10, 最終更新日: 2024-11-06)

主引用文献

Boehm, M.K.,Corper, A.L.,Wan, T.,Sohi, M.K.,Sutton, B.J.,Thornton, J.D.,Keep, P.A.,Chester, K.A.,Begent, R.H.J.,Perkins, S.J.
Crystal Structure of the Anti-Carcinoembryonic Antigen Single-Chain Fv Antibody Mfe-23 and a Model for Antigen Binding Based on Intermolecular Contacts
Biochem.J., 346:519-, 2000

PubMed Abstract: MFE-23 is the first single-chain Fv antibody molecule to be used in patients and is used to target colorectal cancer through its high affinity for carcinoembryonic antigen (CEA), a cell-surface member of the immunoglobulin superfamily. MFE-23 contains an N-terminal variable heavy-chain domain joined by a (Gly(4)Ser)(3) linker to a variable light-chain (V(L)) domain (kappa chain) with an 11-residue C-terminal Myc-tag. Its crystal structure was determined at 2.4 A resolution by molecular replacement with an R(cryst) of 19.0%. Five of the six antigen-binding loops, L1, L2, L3, H1 and H2, conformed to known canonical structures. The sixth loop, H3, displayed a unique structure, with a beta-hairpin loop and a bifurcated apex characterized by a buried Thr residue. In the crystal lattice, two MFE-23 molecules were associated back-to-back in a manner not seen before. The antigen-binding site displayed a large acidic region located mainly within the H2 loop and a large hydrophobic region within the H3 loop. Even though this structure is unliganded within the crystal, there is an unusually large region of contact between the H1, H2 and H3 loops and the beta-sheet of the V(L) domain of an adjacent molecule (strands DEBA) as a result of intermolecular packing. These interactions exhibited remarkably high surface and electrostatic complementarity. Of seven MFE-23 residues predicted to make contact with antigen, five participated in these lattice contacts, and this model for antigen binding is consistent with previously reported site-specific mutagenesis of MFE-23 and its effect on CEA binding.

PubMed: 10677374
DOI: 10.1042/0264-6021:3460519

実験手法

X-RAY DIFFRACTION (2.4 Å)