The 1.2 A resolution structure of the Con A-dimannose complex

Area of Science:

• Carbohydrate chemistry
• Structural biology
• Biochemistry

Background:

• Concanavalin A (Con A) is a plant lectin that binds to mannose and glucose residues.
• Understanding sugar-protein interactions is crucial for various biological processes and drug development.
• Previous studies on Con A-carbohydrate complexes lacked atomic-level detail.

Purpose of the Study:

• To elucidate the atomic details of the interaction between Con A and alpha1-2 mannobiose.
• To provide insights into the molecular basis for the high affinity of Con A to specific mannose linkages.
• To improve computational models of sugar-protein interactions.

Main Methods:

• X-ray crystallography of the Con A-alpha1-2 mannobiose complex.
• Structure refinement to 1.2 Å resolution, the highest for a sugar-lectin complex.
• Difference density map analysis to model hydrogen atoms and identify key residues.

Main Results:

• The structure reveals a protonated Asp208 residue involved in hydrogen bonding with alpha1-2 mannobiose.
• This protonation state differs from the native Con A structure (0.94 Å resolution).
• The observed interactions explain the preferential binding of alpha1-2 linked mannose over other disaccharides.

Conclusions:

• The protonated Asp208 is essential for the high affinity of Con A to alpha1-2 mannobiose.
• The high-resolution structural data challenge previous predictions from modeling studies.
• This work provides critical data for refining sugar-protein interaction modeling algorithms.