NMR in Glycoscience and Glycotechnology
CHAPTER 12: Solid-State NMR Analysis of Mannose Recognition by Pradimicin A
Published:15 May 2017
Special Collection: 2017 ebook collectionSeries: New Developments in NMR
Y. Nakagawa and Y. Ito, in NMR in Glycoscience and Glycotechnology, ed. K. Kato and T. Peters, The Royal Society of Chemistry, 2017, pp. 269-289.
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Pradimicin A (PRM-A) is a unique natural product having a lectin-like ability to recognize d-mannose (d-Man) in the presence of Ca2+ ion. Despite its great potential as biochemical tools and therapeutic leads, the molecular basis of d-Man recognition by PRM-A has been scarcely investigated. The problem lies in aggregative propensity of PRM-A and formation of multiple complexes with Ca2+ ion and d-Man, which have frustrated X-ray crystallographic and conventional solution NMR analyses. This situation led us to explore a novel analytical strategy using solid-state NMR spectroscopy. The key to our strategy is the use of the solid aggregates solely composed of the simple 1 : 1 complex of PRM-A and d-Man, which enabled the interaction analysis with avoidance of the problem associated with the complicated complex formation. A combination of the solid-state 113Cd-NMR and two-dimensional dipolar-assisted rotational resonance (2D-DARR) experiments revealed the Ca2+-mediated d-Man-binding geometry of PRM-A, which further led to the finding that PRM-A has the ability to bind d-Man residues other than non-reducing ends of glycans. The present study provides new insights into the molecular basis of d-Man recognition and glycan specificity of PRM-A.