Conserved Active Site Architecture Between Bacterial Cellulose and Chitin Synthases

Area of Science:

• Biochemistry
• Molecular Biology
• Enzymology

Background:

• Glycosyltransferases (GTs) are crucial enzymes synthesizing glycosidic bonds, vital for numerous biological processes.
• Chitin and cellulose synthases are integral membrane GTs synthesizing structural polysaccharides chitin and cellulose.
• These enzymes are typically considered to have strict substrate specificity.

Purpose of the Study:

• To investigate the active site conservation between bacterial cellulose and chitin synthases.
• To explore the implications of conserved active site motifs on enzyme specificity.
• To propose a new perspective on the catalytic capabilities of these GTs.

Main Methods:

• Bioinformatic analysis of conserved active site motifs in bacterial cellulose and chitin synthases.
• Comparative analysis of sequence and structural similarities among distant bacterial species.
• Theoretical framework development for assessing enzyme promiscuity.

Main Results:

• A common active site motif (E-D-D-ED-QRW-TK) was identified in bacterial cellulose and chitin synthases.
• This motif is spatially co-localized and conserved across diverse bacterial species.
• Low sequence and structural similarity between these synthases contrasts with the conserved active site.

Conclusions:

• Bacterial cellulose and chitin synthases share a conserved active site, suggesting potential catalytic promiscuity.
• This challenges the established notion of strict substrate specificity for these enzymes.
• The findings pave the way for experimental validation of cross-substrate activity in vivo and in silico.