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Classification, characterization and structural analysis of sugar nucleotidylyltransferase family of enzymes.

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Relation http://ir.cftri.com/14652/
https://doi.org/10.1016/j.bbrc.2020.02.148
 
Title Classification, characterization and structural analysis of sugar
nucleotidylyltransferase family of enzymes.
 
Creator Vaibhav Singh, Bais
Pooja, Aggarwal
Prashant, Bharadwaj
Balaji, Prakash
 
Subject 05 Enzymes
25 Sugar/Starch/Confectionery
 
Description Sugar Nucleotidyl Transferases (SNTs) constitute a large family of enzymes that play important metabolic
roles. Earlier, for one such SNT, termed N-acetylglucosamine-1-phosphate uridyltransferase- GlmU, we
had established that two magnesium ions - Mg2þ
A and Mg2þ
B - catalyze the sugar-nucleotidyl transfer
reaction. Despite a common structural framework that SNTs share, we recognized key differences around
the active-site based on the analysis of available structures. Based on these differences, we had classified
SNTs into two major groups, Group - I & II; and further, variation in ‘Mg2þ
A-stabilizing motifs’ led us to
sub-classify them into five distinct sub-groups. Since group specific conservation of ‘Mg2þ
A-stabilizing
motifs’ was based only for 45 available structures, here we validate this via an exhaustive analysis of
1,42,025 protein sequences. Previously, we had hypothesized that a metal-ion-catalyzed mechanism
would be operative in all SNTs. Here, we validate it biochemically and establish that Mg2þ is a strict
requirement for nucleotidyl transfer reactions in every group or sub-group and that a common metal ion
dependent mechanism operates in SNTs. Further, mutating Mg2þ
A coordinating residue in each subgroup led to abolished catalysis, indicating an important role for both of these residues and suggest
that SNTs employ variations over ‘a conserved catalytic mechanism mediated by Mg2þ ion(s)’, to bring
about functional diversity. This would constitute a comprehensive study to establish the catalytic
mechanism across the family of SNTs.
 
Date 2020
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/14652/1/Biochemical%20and%20Biophysical%20Research%20Communication%202020.pdf
Vaibhav Singh, Bais and Pooja, Aggarwal and Prashant, Bharadwaj and Balaji, Prakash (2020) Classification, characterization and structural analysis of sugar nucleotidylyltransferase family of enzymes. Biochemical and Biophysical Research Communications, 525 (3). pp. 780-785. ISSN 0006-291X