4JS1

crystal structure of human Beta-galactoside alpha-2,6-sialyltransferase 1 in complex with cytidine and phosphate

Summary for 4JS1

• Entry DOI: 10.2210/pdb4js1/pdb
• Related: 4JS2
• Descriptor: Beta-galactoside alpha-2,6-sialyltransferase 1, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 4-AMINO-1-BETA-D-RIBOFURANOSYL-2(1H)-PYRIMIDINONE, ... (5 entities in total)
• Functional Keywords: rossmann, gt-a, sialyltransferase, glycoprotein, sialylation, endoplasmatic reticulum, golgi, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 38801.58

Authors

Kuhn, B.,Benz, J.,Greif, M.,Engel, A.M.,Sobek, H.,Rudolph, M.G. (deposition date: 2013-03-22, release date: 2013-07-31, Last modification date: 2024-11-20)

Primary citation

Kuhn, B.,Benz, J.,Greif, M.,Engel, A.M.,Sobek, H.,Rudolph, M.G.
The structure of human alpha-2,6-sialyltransferase reveals the binding mode of complex glycans.
Acta Crystallogr.,Sect.D, 69:1826-1838, 2013

PubMed Abstract: Human β-galactoside α-2,6-sialyltransferase I (ST6Gal-I) establishes the final glycosylation pattern of many glycoproteins by transferring a sialyl moiety to a terminal galactose. Complete sialylation of therapeutic immunoglobulins is essential for their anti-inflammatory activity and protein stability, but is difficult to achieve in vitro owing to the limited activity of ST6Gal-I towards some galactose acceptors. No structural information on ST6Gal-I that could help to improve the enzymatic properties of ST6Gal-I for biotechnological purposes is currently available. Here, the crystal structures of human ST6Gal-I in complex with the product cytidine 5'-monophosphate and in complex with cytidine and phosphate are described. These complexes allow the rationalization of the inhibitory activity of cytosine-based nucleotides. ST6Gal-I adopts a variant of the canonical glycosyltransferase A fold and differs from related sialyltransferases by several large insertions and deletions that determine its regiospecificity and substrate specificity. A large glycan from a symmetry mate localizes to the active site of ST6Gal-I in an orientation compatible with catalysis. The glycan binding mode can be generalized to any glycoprotein that is a substrate of ST6Gal-I. Comparison with a bacterial sialyltransferase in complex with a modified sialyl donor lends insight into the Michaelis complex. The results support an SN2 mechanism with inversion of configuration at the sialyl residue and suggest substrate-assisted catalysis with a charge-relay mechanism that bears a conceptual similarity to serine proteases.

PubMed: 23999306
DOI: 10.1107/S0907444913015412

Experimental method

X-RAY DIFFRACTION (2.09 Å)