PDBsum entry 1mfd

Immunoglobulin

PDB id: 1mfd

Contents

Protein chains

212 a.a. *

212 a.a. *

Ligands

MMA-GLA-ABE

Waters ×85

* Residue conservation analysis

PDB id:

1mfd

Name:

Immunoglobulin

Title:

The solution structure of a trisaccharide-antibody complex: comparison of nmr measurements with a crystal structure

Structure:

Igg1-lambda se155-4 fab (light chain). Chain: l. Engineered: yes. Igg1-lambda se155-4 fab (heavy chain). Chain: h. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.183

Authors:

A.Zdanov,M.Cygler

Key ref:

D.R.Bundle et al. (1994). Solution structure of a trisaccharide-antibody complex: comparison of NMR measurements with a crystal structure. Biochemistry, 33, 5183-5192. PubMed id: 8172893 DOI: 10.1021/bi00183a023

Date:

25-Oct-93 Release date: 31-Jan-94

Protein chain

No UniProt id for this chain

Struc: 212 a.a.

Protein chain

No UniProt id for this chain

Struc: 212 a.a.

DOI no: 10.1021/bi00183a023

Biochemistry 33:5183-5192 (1994)

PubMed id: 8172893

Solution structure of a trisaccharide-antibody complex: comparison of NMR measurements with a crystal structure.

D.R.Bundle, H.Baumann, J.R.Brisson, S.M.Gagné, A.Zdanov, M.Cygler.

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.