Hyaluronan synthases: fascinating glycosyltransferases from vertebrates, bacterial pathogens, and algal viruses

DeAngelis, Paul L.

doi:10.1007/s000180050461

Cited by 182 publications

(136 citation statements)

References 60 publications

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“…infected by the Chlorovirus [49,83]-, yeasts such as Cryptococcus neoformans- [49] and molluscs [84]. However, it is not found in fungi, plants and insects [85].…”

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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Since its first isolation in 1934, hyaluronic acid (HA) has been studied across a variety of research areas. This unbranched glycosaminoglycan consisting of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid is almost ubiquitary in humans and in other vertebrates. HA is involved in many key processes -including cell signaling, wound reparation, tissue regeneration, morphogenesis, matrix organization and pathobiology-, and has unique physico-chemical properties -such as biocompatibility, biodegradability, mucoadhesivity, hygroscopicity and viscoelasticity. For these reasons, exogenous HA has been investigated as drug delivery system and treatment in cancer, ophthalmology, arthrology, pneumology, rhinology, urology, aesthetic medicine and cosmetic. To improve and customize its properties and applications, HA can be subjected to chemical modifications: conjugation and crosslinking. The present review gives an overview regarding HA, describing its history, physico-chemical, structural and hydrodynamic properties, and biology -occurrence, biosynthesis (by hyaluronan synthases), degradation (by hyaluronidases and oxidative stress), roles, mechanisms of action and receptors. Furthermore, both conventional and recently emerging methods developed for the industrial production of HA and its chemical derivatization are presented. Finally, the medical, pharmaceutical and cosmetic applications of HA and its derivatives are reviewed, reporting examples of HA-based products which currently are on the market or are undergoing further investigations.

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“…infected by the Chlorovirus [49,83]-, yeasts such as Cryptococcus neoformans- [49] and molluscs [84]. However, it is not found in fungi, plants and insects [85].…”

Section: Ha Occurrence In Living Organism and Diffusion In Human Bodymentioning

confidence: 99%

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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“…More vertebrate isozymes with similar amino acid sequences were subsequently identified [7,8]. In addition, a HAS from an algal virus, CvHAS, was also discovered [7,9].…”

Section: Introductionmentioning

confidence: 95%

“…A Xenopus laevis (African clawed frog) protein, XlHAS1, originally called DG42, was the first vertebrate HA synthase to be cloned as an abundant transcript during gastrulation, but at the time its function was not known [4][5][6]. More vertebrate isozymes with similar amino acid sequences were subsequently identified [7,8]. In addition, a HAS from an algal virus, CvHAS, was also discovered [7,9].…”

Section: Introductionmentioning

confidence: 99%

The functional molecular mass of the Pasteurella hyaluronan synthase is a monomer

Pummill¹,

Kane²,

Kempner

et al. 2007

Biochimica et Biophysica Acta (BBA) - General Subjects

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Hyaluronan (HA), a linear polysaccharide composed of β1,3-GlcNAc-β1,4-GlcUA repeats, is found in the extracellular matrix of vertebrate tissues as well as the capsule of several pathogenic bacteria. All known HA synthases (HASs) are dual-action glycosyltransferases that catalyze the addition of two different sugars from UDP-linked precursors to the growing HA chain. The bacterial hyaluronan synthase, PmHAS from Gram-negative Pasteurella multocida, is a 972-residue membraneassociated protein. Previously, the Gram-positive Streptococcus pyogenes enzyme, SpHAS (419 residues), and the vertebrate enzyme, XlHAS1 (588 residues), were found to function as monomers of protein, but the PmHAS is not similar at the protein sequence level and has quite different enzymological properties. We have utilized radiation inactivation to measure the target size of recombinant full-length and truncated PmHAS. The target size of HAS activity was confirmed using internal enzyme standards of known molecular weight. We found that the Pasteurella HA synthase protein functions catalytically as a monomer. Functional truncated soluble PmHAS also behaves as a polypeptide monomer as assessed by gel filtration chromatography and light scattering.

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“…HA is necessary for normal development in vertebrates and plays important functions in normal and in disease situations (1)(2)(3)(4)(5)(6)(7). Since the discovery and cloning in 1993 of the first gene encoding an HA synthase (HAS), the spHAS from Streptococcus pyogenes (8), similar HA synthase genes (or cDNAs) have been identified in mammals (e.g., humans and mice), frogs, and even in a virus that infects an alga, which in turn lives Abbreviations: GlcA, D-glucuronic acid; GlcNAc, N -acetyl D-glucosamine; HA, hyaluronan; HAS, hyaluronan synthase; UDP-GlcA, uridine 5 -diphosphate D-glucuronic acid; UDP-GlcNAc, uridine 5 -diphosphate N -acetyl D-glucosamine. in a protozoan host (9)(10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

“…These various HAS enzymes comprise a large family of proteins with many common features and regions of amino acid sequence identity or similarity. Based on their similarities and differences, the known HAS proteins have been divided into two categories, designated Class I and Class II (2). So far, the HAS from Pasteurella multocida (pmHAS) is the only Class II member and is quite different from all other HASs.…”

Section: Introductionmentioning

confidence: 99%

Functional Characteristics and Catalytic Mechanisms of the Bacterial Hyaluronan Synthases

Weigel

2002

IUBMB Life

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SummaryThe first gene for a glycosaminoglycan synthase to be cloned was the hyaluronan (HA) synthase from S. pyogenes, which we reported in 1993. Since then, at least 20 bacterial, viral, or eukaryotic HA synthase gene or cDNA sequences and two bacterial chondroitin synthase genes have been reported. During the last decade a great deal has been elucidated about the structure, function, and mechanisms of action of the bacterial HA synthases, which are the focus of this review. Very rapid progress has been made in elucidating the mechanism of HA synthesis by the HA synthase from Pasteurella multocida. Although little of this information is applicable to understanding the mechanism of action of streptococcal HA synthases, good progress has also been made in understanding how these latter enzymes work. Keywords Hyaluronan; hyaluronan synthase; hyaluronic acid; pasteurella hyaluronan synthase; streptococcus hyaluronan synthase.

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Hyaluronan synthases: fascinating glycosyltransferases from vertebrates, bacterial pathogens, and algal viruses

Cited by 182 publications

References 60 publications

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

The functional molecular mass of the Pasteurella hyaluronan synthase is a monomer

Functional Characteristics and Catalytic Mechanisms of the Bacterial Hyaluronan Synthases

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