Hyaluronan synthases: fascinating glycosyltransferases from vertebrates, bacterial pathogens, and algal viruses.
Hyaluronan (or hyaluronic acid or hyaluronate; HA) is a polysaccharide found in the extracellular matrix of vertebrate tissues and in the surface coating of certain Streptococcus and Pasteurella bacterial pathogens. At least one algal virus directs its host to produce HA on the cell surface early in infection. HA synthases (HASs) are the enzymes that polymerize HA using uridine diphospho-sugar precursors. In all known cases, HA is secreted out of the cell; therefore, HASs are normally found in the outer membranes of the organism. In the last 6 years, the HASs have been molecularly cloned from all the above sources. They were the first class of glycosyltransferases identified in which a single polypeptide species catalyzes the transfer of two different monosaccharides; this finding is in contrast to the usual 'single enzyme, single sugar' dogma of glycobiology. There appear to be two distinct classes of HASs based on differences in amino acid sequence, topology in the membrane, and reaction mechanism. This review discusses the current state of knowledge surrounding the molecular details of HA biosynthesis and summarizes the possible evolutionary history of the HASs.
DeAngelis
P L
PL
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA. paul-deangelis@OUHSC.edu
D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology* / Q000472:pathogenicity; D056890:Eukaryota / Q000821:virology*; D019143:Evolution, Molecular; D014453:Glucuronosyltransferase / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016695:Glycosyltransferases; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D050356:Lipid Metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D014166:Transferases; D014714:Vertebrates; D014780:Viruses / Q000201:enzymology*; D029867:Xenopus Proteins
D008565:Membrane Proteins; D009844:Oligosaccharides; D029867:Xenopus Proteins; D006820:Hyaluronic Acid; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases