Genetic and enzymatic characterization of 3-O-sulfotransferase SNPs associated with Plasmodium falciparum parasitaemia

Ngoc, Nguyen Huy; Vivès, Romain R.; Torres, Magali; Delauzun, Vincent; Saesen, Els; Roig-Zamboni, V.; Lortat‐Jacob, Hugues; Rihet, Pascal; Bourne, Yves

doi:10.1093/glycob/cwy038

Cited by 5 publications

(1 citation statement)

References 30 publications

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“…Moreover, 3- O -sulfated HS (3S-HS) are well known to increase susceptibility to infection by pathogens 12 . Accordingly, polymorphism in both HS3ST3A1 and HS3STB1 has been associated with risk to P. falciparum infection 173 and some 3S-HS structures trigger HSV infection 12 .…”

Section: Resultsmentioning

confidence: 99%

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Ouidja

Biard

Chantepie

et al. 2022

Preprint

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Proteoglycans are complex macromolecules formed of glycosaminoglycan chains covalently linked to core proteins through a linker tetrasaccharide common to heparan sulfate proteoglycans (HSPG) and chondroitin sulfate proteoglycans (CSPG). Biosynthesis of a single proteoglycan requires the expression of dozens of genes, which together create the large structural and functional diversity reflected by the numerous diseases or syndromes associated to their genetic variability. Among proteoglycans, HSPG are the most structurally and functionally complex. To decrease this complexity, we retrieved and linked information on pathogenic variants, polymorphism, expression, and literature databases for 50 genes involved in the biosynthesis of HSPG core proteins, heparan sulfate (HS) chains, and their linker tetrasaccharide. This resulted in a new gene organization and biosynthetic pathway representation in which the phenotypic continuum of disorders as linkeropathies and other pathologies could be predictable. Moreover, ubiquitous NDST1, GLCE, HS2ST1, and HS6ST1 appeared to generate ubiquitous heparan sulfate (HS) sequences essential for normal development and homeostasis, whereas the tissue restricted NDST2-4, HS6ST2-3, and HS3ST1-6 appeared to generate specialized HS sequences mainly involved in responsiveness to stimuli. Supported by data on genetic polymorphism and clinical variants, we afford a new vision of HSPG involvement in homeostasis, disease, vulnerability to disease, and behavioral disorders.

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Section: Resultsmentioning

confidence: 99%

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Ouidja

Biard

Chantepie

et al. 2022

Preprint

View full text Add to dashboard Cite

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Genome-wide association study of white matter hyperintensity volume in elderly persons without dementia

Guo

Shen

Hou

et al. 2020

NeuroImage: Clinical

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From Steroid and Drug Metabolism to Glycobiology, Using Sulfotransferase Structures to Understand and Tailor Function

Pedersen

et al. 2022

Drug Metab Dispos

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Sulfotransferases are ubiquitous enzymes that transfer a sulfo group (SO 3 ) from the universal cofactor donor PAPS to a broad range of acceptor substrates. In humans, the cytosolic sulfotransferases (SULTs) are involved in the sulfation of endogenous compounds such as steroids, neurotransmitters, hormones and bile acids as well as xenobiotics including drugs, toxins and environmental chemicals. The Golgi associated membrane-bound sulfotransferases are involved in post-translational modification of macromolecules from glycosaminoglycans to proteins. The sulfation of small molecules can have profound biological effects on the functionality of the acceptor, including activation, deactivation or enhanced metabolism and elimination. Sulfation of macromolecules has been shown to regulate a number of physiological and pathophysiological pathways by enhancing binding affinity to regulatory proteins or binding partners. Over the last 25 years, crystal structures of these enzymes have provided a wealth of information on the mechanisms of this process and the specificity of these enzymes. This review will focus on the general commonalities of the sulfotransferases, from enzyme structure to catalytic mechanism as well as providing examples into how structural information is being utilized to either design drugs that inhibit sulfotransferases or to modify the enzymes to improve drug synthesis.

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Genetic and enzymatic characterization of 3-O-sulfotransferase SNPs associated with Plasmodium falciparum parasitaemia

Cited by 5 publications

References 30 publications

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Genome-wide association study of white matter hyperintensity volume in elderly persons without dementia

From Steroid and Drug Metabolism to Glycobiology, Using Sulfotransferase Structures to Understand and Tailor Function

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