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A novel C-domain-dependent inhibition of the rainbow trout CMP-sialic acid synthetase activity by CMP-deaminoneuraminic acid.

Authors :
Wu, Di
Gilormini, Pierre-André
Toda, Sakura
Biot, Christophe
Lion, Cédric
Guérardel, Yann
Sato, Chihiro
Kitajima, Ken
Source :
Biochemical & Biophysical Research Communications. Aug2022:Part 1, Vol. 617, p16-21. 6p.
Publication Year :
2022

Abstract

The CMP-sialic acid synthetase (CSS) activates free sialic acid (Sia) to CMP-Sia using CTP, and is prerequisite for the sialylation of cell surface glycoconjugates. The vertebrate CSS consists of two domains, a catalytic N-domain and a non-catalytic C-domain. Although the C-domain is not required for the CSS enzyme to synthesize CMP-Sia, its involvement in the catalytic activity remains unknown. First, the real-time monitoring of CSS-catalyzed reaction was performed by 31P NMR using the rainbow trout CSS (rtCSS). While a rtCSS lacking the C-domain (rtCSS-N) similarly activated both deaminoneuraminic acid (Kdn) and N -acetylneuraminic acid (Neu5Ac), the full-length rtCSS (rtCSS-FL) did not activate Kdn as efficiently as Neu5Ac. These results suggest that the C-domain of rtCSS affects the enzymatic activity, when Kdn was used as a substrate. Second, the enzymatic activity of rtCSS-FL and rtCSS-N was measured under various concentrations of CMP-Kdn. Inhibition by CMP-Kdn was observed only for rtCSS-FL, but not for rtCSS-N, suggesting that the inhibition was C-domain-dependent. Third, the inhibitory effect of CMP-Kdn was also investigated using the mouse CSS (mCSS). However, no inhibition was observed with mCSS even at high concentrations of CMP-Kdn. Taken together, the data demonstrated that the C-domain is involved in the CMP-Kdn-dependent inhibition of rtCSS, which is a novel regulation of the Sia metabolism in rainbow trout. • The rainbow trout CMP-sialic acid synthetase rtCSS can use a unique sialic acid Kdn. • rtCSS consists of a catalytic N-domain and a non-catalytic C-domain of unknown role. • in situ Monitoring of rtCSS reaction by 31P NMR finds the C-domain-dependent anomaly. • CMP-Kdn, but not CMP-Neu5Ac, inhibits rtCSS in a C-domain-dependent manner. • The CMP-Kdn-specific C-domain-dependent inhibition is unique to Kdn metabolism. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0006291X
Volume :
617
Database :
Academic Search Index
Journal :
Biochemical & Biophysical Research Communications
Publication Type :
Academic Journal
Accession number :
157438106
Full Text :
https://doi.org/10.1016/j.bbrc.2022.05.031