Analysis and validation of carbohydrate three-dimensional structures

Abstract

Knowledge of the three-dimensional structures of the carbohydrate molecules is indispensable for a full understanding of the molecular processes in which carbohydrates are involved, such as protein glycosylation or protein-carbohydrate interactions. The Protein Data Bank (PDB) is a valuable resource for three-dimensional structural information on glycoproteins and protein-carbohydrate complexes. Unfortunately, many carbohydrate moieties in the PDB contain inconsistencies or errors. This article gives an overview of the information that can be obtained from individual PDB entries and from statistical analyses of sets of three-dimensional structures, of typical problems that arise during the analysis of carbohydrate three-dimensional structures and of the validation tools that are currently available to scientists to evaluate the quality of these structures.

The Solution Structure of Heparan Sulfate Differs from That of Heparin

“…The PDB structure 2JCR (from the same study as PDB code 2JCQ) uses the correct term BDP. Related discrepancies in the PDB have also been reported by others (54, 59). …”

3DSDSCAR—a three dimensional structural database for sialic acid-containing carbohydrates through molecular dynamics simulation

“…Carbohydrate moieties of many of the protein carbohydrate complexes that are available in PDB contain errors in their structures. 71 For example, the 3D structure of Clostridium botulinum neurotoxin B complexed with sialyllactose is solved through X-ray crystallographic technique and is available in the Protein databank with the ID 1f31. 72 A careful analysis of the carbohydrate moiety reveals that the orientation of hydroxyl groups at C-3 and C-6 positions of galactose is not correct.…”

Computational glycoscience: characterizing the spatial and temporal properties of glycans and glycan–protein complexes

“…rather than to derive 3D structures from sparse experimental data [20]. Further, as noted by Lütteke [52], there is unusually high level of structural and annotation errors in the X-ray structures of carbohydrate–protein complexes and glycoproteins. These errors arise in part from limitations in carbohydrate residue and linkage nomenclature [53] employed in the Protein Data Bank (http://www.rcsb.org/pdb/), as well as from a lack of adoption of carbohydrate-specific tools for structure curation or refinement validation [54].…”