Towars a unified methodology to validate glycoproteins

GARAY PABLO G.; MARTIN OSVALDO O.; ICAZATTI ALEJANDRO A.; VILA JORGE A.; SCHERAGA HAROLD A.; ARNAUTOVA YELENA A.

Rosario

Workshop; Taller Fronteras en Resonancia Magnética, de los Materiales a los Sistemas Biológicos.; 2013

Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET)

Over the last several years we have focused our efforts in developing computational tools, such as the CheShift-2 server (Vila et al., 2009, Martin et al., 2012, Martin et al., 2013), for automated validation of X-ray and NMR determined protein structures, provided that the observed 13C and/or 13C chemical shifts are available. More than 50% of known protein are glycoproteins (Apweiler et al., 1999), although only 3.5% of the proteins deposited in the the Protein Data Bank (PDB, Bernstein et al., 1977) are covalently bound to a glycan chain and thus can be classified as glycoproteins (Lütteke, 2009). There are multiple reasons why the PDB is heavily biased against glycoproteins, among others the following: glycan chains often hamper crystal growth and, hence, they are removed before-hand, carbohydrates are very flexible molecules and therefore often do not yield sufficient electron density to resolve the three-dimensional structure, etc. (Lütteke, 2009). In addition, around 30% of the PDB-deposited carbohydrates entries contain errors (Lütteke, 2009). Overall, the need for accurate and fast validation methods to detect flaws in protein/glycan structures, at residue/disaccharide level, appears to be crucial. Consequently, here we present a summary of the main features of the CheShift-2 server (Martin et al., 2013) for protein structure validation and also the first steps to expand our methodology to include validation of glycans.