Quantum Mechanics/Molecular Mechanics Study of the Sialyltransferase Reaction Mechanism

The sialyltransferase is an enzyme that transfers the sialic acid moiety from cytidine 5′-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of glycans. To elucidate the catalytic mechanism of sialyltransferase, we explored the potential energy surface along the sialic acid tr...

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Bibliographic Details
Published in:Biochemistry (Easton) 2016-10, Vol.55 (40), p.5764-5771
Main Authors: Hamada, Yojiro, Kanematsu, Yusuke, Tachikawa, Masanori
Format: Article
Language:English
Subjects:
Protein Conformation
Quantum Theory
Sialyltransferases - chemistry
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Summary:The sialyltransferase is an enzyme that transfers the sialic acid moiety from cytidine 5′-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of glycans. To elucidate the catalytic mechanism of sialyltransferase, we explored the potential energy surface along the sialic acid transfer reaction coordinates by the hybrid quantum mechanics/molecular mechanics method on the basis of the crystal structure of sialyltransferase CstII. Our calculation demonstrated that CstII employed an SN1-like reaction mechanism via the formation of a short-lived oxocarbenium ion intermediate. The computational barrier height was 19.5 kcal/mol, which reasonably corresponded with the experimental reaction rate. We also found that two tyrosine residues (Tyr156 and Tyr162) played a vital role in stabilizing the intermediate and the transition states by quantum mechanical interaction with CMP.
ISSN:0006-2960
1520-4995
DOI:10.1021/acs.biochem.6b00267