Date Published: April 01, 2019
Publisher: International Union of Crystallography
Author(s): Bart van Beusekom, Natasja Wezel, Maarten L. Hekkelman, Anastassis Perrakis, Paul Emsley, Robbie P. Joosten.
Carbohydrates are automatically built and rebuilt using Coot in the PDB-REDO pipeline.
Proteins are frequently regulated by post-translational modifications. One of the most common forms of such modifications is glycosylation (Zhang et al., 2016 ▸); however, this is also one of the most complex forms. Glycans fulfill important roles in several biological processes, such as protein folding, stability and the recognition of other compounds (Varki & Lowe, 2010 ▸). They also greatly influence cancer progression and treatment, for instance by modifying the functionality of cell-surface receptors and adhesion molecules (Taniguchi & Kizuka, 2015 ▸).
All methods were developed specifically for N-glycosylation, and not O-glycosylation, because this is the most prevalent and straightforward type of glycosylation and because the carbohydrate module in Coot (Emsley & Crispin, 2018 ▸), which is used extensively in this work, currently only deals with N-glycosylation.
Building carbohydrates in protein structure models has been difficult, in part owing to a lack of suitable computational tools. Therefore, the structural quality of carbohydrates has traditionally been poor. Recently, much improved tools for carbohydrate building have become available. This motivated us to apply them to existing protein structure models to make improved structure models available for glycosylated protein structures determined in the past and to simultaneously make these tools available to crystallographers via an automated web server.
Both the PDB-REDO databank and web server are hosted at https://pdb-redo.eu. Crystallographers can submit work-in-progress models on the web server to run PDB-REDO including the carbohydrate-building procedure. The 1978 models from the test set are available through the databank. Other databank entries will be updated gradually to include the carbohydrate-building procedure. On the PDB-REDO databank entry pages, registered users can submit an update request to prioritize the update of that entry. Binary executables for Carbivore, Carbonanza and stats are available from the PDB-REDO website and the source code is available on request. Non-graphics-dependent carbohydrate modeling in Coot has been available since June 2018.