1MFD

THE SOLUTION STRUCTURE OF A TRISACCHARIDE-ANTIBODY COMPLEX: COMPARISON OF NMR MEASUREMENTS WITH A CRYSTAL STRUCTURE

1MFD の概要

• エントリーDOI: 10.2210/pdb1mfd/pdb
• 分子名称: IGG1-LAMBDA SE155-4 FAB (LIGHT CHAIN), IGG1-LAMBDA SE155-4 FAB (HEAVY CHAIN), alpha-D-galactopyranose-(1-2)-[alpha-D-Abequopyranose-(1-3)]methyl alpha-D-mannopyranoside, ... (4 entities in total)
• 機能のキーワード: immunoglobulin
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47182.56

構造登録者

Zdanov, A.,Cygler, M. (登録日: 1993-10-25, 公開日: 1994-01-31, 最終更新日: 2024-10-30)

主引用文献

Bundle, D.R.,Baumann, H.,Brisson, J.R.,Gagne, S.M.,Zdanov, A.,Cygler, M.
Solution structure of a trisaccharide-antibody complex: comparison of NMR measurements with a crystal structure.
Biochemistry, 33:5183-5192, 1994

PubMed Abstract: NMR and crystallography have been used to study antigen conformational changes that occur in a trisaccharide-Fab complex in solution and in the solid state. NOE buildup rates from transferred NOE experiments show that the antigenic determinant of a Salmonella lipopolysaccharide, represented by the trisaccharide methyl glycoside alpha-D-Galp(1-->2 [alpha-D-Abep(1-->3)]- alpha-D-Manp1-->OMe (1), undergoes a protein-induced conformational shift about the Gal-->Man glycosidic linkage when it is bound by a monoclonal antibody in aqueous solution. The same trisaccharide was crystallized with Fab, and a solved structure at 2.1-A resolution revealed that the conformation of the trisaccharide ligand was similar to that seen in a dodesaccharide-Fab complex [Cygler et al. (1991) Science 253, 442-445), where the Gal-Man linkage also experienced a similar conformational shift. Distance constraints derived from the TRNOE buildup curves are consistent with two bound trisaccharide conformations, one of which correlates with the ligand conformation of the crystalline Fab-trisaccharide complex. In this bound conformation, short interatomic distances between Abe O-2 and Gal O-2 permit an oligosaccharide intramolecular hydrogen bond. Despite its relatively low energy, a preponderance of this conformer could not be detected in aqueous or DMSO solutions of free trisaccharide by either 1H or 13C NMR experiments. In DMSO, a different intramolecular hydrogen bond between Abe O-2 and Man O-4 was observed due to a solvent-induced shift in the conformational equilibria (relative to aqueous solution). Molecular modeling of the trisaccharide in the binding site and as the free ligand suggested that the protein imposes an induced fit on the antigen, primarily resulting in a shift of the Gal-Man phi torsional angle. This reduces the interproton separation between Abe H-3 and Gal H-1 with a marked increase in the intensity of the previously weak NOEs between the protons of the noncovalently linked galactose and abequose residues. The impact of the conformational shift on gross trisaccharide topology is sufficiently small that binding modes inferred from functional group replacements are not impaired.

PubMed: 8172893
DOI: 10.1021/bi00183a023

実験手法

X-RAY DIFFRACTION (2.1 Å)