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CMP-Sialic Acid Synthetase: The Point of Constriction in the Sialylation Pathway

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SialoGlyco Chemistry and Biology I

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 366))

Abstract

Sialoglycoconjugates form the outermost layer of animal cells and play a crucial role in cellular communication processes. An essential step in the biosynthesis of sialylated glycoconjugates is the activation of sialic acid to the monophosphate diester CMP-sialic acid. Only the activated sugar is transported into the Golgi apparatus and serves as a substrate for the linkage-specific sialyltransferases. Interference with sugar activation abolishes sialylation and is embryonic lethal in mammals. In this chapter we focus on the enzyme catalyzing the activation of sialic acid, the CMP-sialic acid synthetase (CMAS), and compare the enzymatic properties of CMASs isolated from different species. Information concerning the reaction mechanism and active site architecture is included. Moreover, the unusual nuclear localization of vertebrate CMASs as well as the biotechnological application of bacterial CMAS enzymes is addressed.

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Abbreviations

BbeCMAS:

CMAS from Branchiostoma belcheri

BtaCMAS:

CMAS from Bos taurus

CKS:

CMP-3-deoxy-d-manno-octulosonic acid synthetase

CMAS:

Cytidine monophosphate N-acetylneuraminic acid synthetase

CthCMAS:

CMAS from Clostridium thermocellum

DmeCMAS:

CMAS from Drosophila melanogaster

DreCMAS:

CMAS from Danio rerio

EcoCMAS:

CMAS from Escherichia coli

HduCMAS:

CMAS from Haemophilus ducreyi

KDN:

Deaminated neuraminic acid

KDO:

3-Deoxy-d-manno-octulosonic acid

MhaCMAS:

CMAS from Mannheimia haemolytica

MmuCMAS:

CMAS from Mus musculus

Neu5Ac:

N-Acetyl-neuraminic acid

Neu5Gc:

N-Glycolyl-neuraminic acid

NmeCMAS:

CMAS from Neisseria meningitidis

OmyCMAS:

CMAS from Oncorhynchus mykiss

PAF-AH:

Platelet-activating factor acetylhydrolase

PmuCMAS:

CMAS from Pasteurella multocida

SagCMAS:

CMAS from Streptococcus agalactiae

Sia:

Sialic acid

SsuCMAS:

CMAS from Streptococcus suis

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Acknowledgments

We are grateful to Rita Gerardy-Schahn for generous and continuous support. A.M.-K. acknowledges financial support from the German Research Foundation (DFG; MU1849/1) and M.S. was supported by funding from the DFG (GE 801/6-3,/8-3,/10-1).

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  1. Institute for Cellular Chemistry, Hannover Medical School (MHH), Hannover, 30625, Germany

    Melanie Sellmeier, Birgit Weinhold & Anja Münster-Kühnel

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  1. Melanie Sellmeier
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Correspondence to Anja Münster-Kühnel .

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Sellmeier, M., Weinhold, B., Münster-Kühnel, A. (2013). CMP-Sialic Acid Synthetase: The Point of Constriction in the Sialylation Pathway. In: SialoGlyco Chemistry and Biology I. Topics in Current Chemistry, vol 366. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2013_477

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