title: Carbohydrate-active enzymes: sequences, shapes, contortions and cells.
abstract: The enzyme-catalysed degradation of oligo and polysaccharides is of considerable interest in many fields ranging from the fundamental-understanding the intrinsic chemical beauty-through to the applied, including diverse practical applications in medicine and biotechnology. Carbohydrates are the most stereochemically-complex biopolymer, and myriad different natural polysaccharides have led to evolution of multifaceted enzyme consortia for their degradation. The glycosidic bonds that link sugar monomers are among the most chemically-stable, yet enzymatically-labile, bonds in the biosphere. That glycoside hydrolases can achieve a rate enhancement (kcat/kuncat) >10(17)-fold provides testament to their remarkable proficiency and the sophistication of their catalysis reaction mechanisms. The last two decades have seen significant advances in the discovery of new glycosidase sequences, sequence-based classification into families and clans, 3D structures and reaction mechanisms, providing new insights into enzymatic catalysis. New impetus to these studies has been provided by the challenges inherent in plant and microbial polysaccharide degradation, both in the context of environmentally-sustainable routes to foods and biofuels, and increasingly in human nutrition. Study of the reaction mechanism of glycoside hydrolases has also inspired the development of enzyme inhibitors, both as mechanistic probes and increasingly as therapeutic agents. We are on the cusp of a new era where we are learning how to dovetail powerful computational techniques with structural and kinetic data to provide an unprecedented view of conformational details of enzyme action.
authors: Structural Biology Laboratory, Department of Chemistry, The University of York, York YO10 5DD, U.K. gideon.davies@york.ac.uk.
authors: Gideon J
authors: GJ
authors: Davies
authors: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors: Spencer J
authors: SJ
authors: Williams
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D050260:Carbohydrate Metabolism; D023281:Genomics; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D006026:Glycoside Hydrolases
keywords: biofuels; conformational analysis; drug design; glycobiology; glycosidase; structural biology