Exploring molecular determinants of polysaccharide lyase family 6-1 enzyme activity

Glycobiology. 2021 Dec 18;31(11):1557-1570. doi: 10.1093/glycob/cwab073.

Abstract

The polysaccharide lyase family 6 (PL6) represents one of the 41 polysaccharide lyase families classified in the CAZy database with the vast majority of its members being alginate lyases grouped into three subfamilies, PL6_1-3. To decipher the mode of recognition and action of the enzymes belonging to subfamily PL6_1, we solved the crystal structures of Pedsa0632, Patl3640, Pedsa3628 and Pedsa3807, which all show different substrate specificities and mode of action (endo-/exolyase). Thorough exploration of the structures of Pedsa0632 and Patl3640 in complex with their substrates as well as docking experiments confirms that the conserved residues in subsites -1 to +3 of the catalytic site form a common platform that can accommodate various types of alginate in a very similar manner but with a series of original adaptations bringing them their specificities of action. From comparative studies with existing structures of PL6_1 alginate lyases, we observe that in the right-handed parallel β-helix fold shared by all these enzymes, the substrate-binding site harbors the same overall conserved structures and organization. Despite this apparent similarity, it appears that members of the PL6_1 subfamily specifically accommodate and catalyze the degradation of different alginates suggesting that this common platform is actually a highly adaptable and specific tool.

Keywords: protein–carbohydrates recognition; structure of alginate lyases; surface-binding site.

MeSH terms

  • Amino Acid Sequence
  • Carbohydrate Conformation
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Polysaccharide-Lyases / chemistry
  • Polysaccharide-Lyases / isolation & purification
  • Polysaccharide-Lyases / metabolism*
  • Substrate Specificity

Substances

  • Polysaccharide-Lyases