HS3ST5

Last update 08 May 2025

Basic Info

Synonyms

3-OST-5, 3OST5, h3-OST-5

+ [6]

Introduction

Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to position 3 of glucosamine residues in heparan. Catalyzes the rate limiting step in the biosynthesis of heparan sulfate (HSact). This modification is a crucial step in the biosynthesis of anticoagulant heparan sulfate as it completes the structure of the antithrombin pentasaccharide binding site. Also generates GlcUA-GlcNS or IdoUA-GlcNS and IdoUA2S-GlcNH2. The substrate-specific O-sulfation generates an enzyme-modified heparan sulfate which acts as a binding receptor to Herpes simplex virus-1 (HSV-1) and permits its entry.

100 Clinical Results associated with HS3ST5

100 Translational Medicine associated with HS3ST5

0 Patents (Medical) associated with HS3ST5

Literatures (Medical) associated with HS3ST5

01 Oct 2024·Hypertension

Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity

Article

Author: Galenkamp, Henrike ; Olde Engberink, Rik H.G. ; Oppelaar, Jetta J. ; Sahebdin, Ghazalah N. ; Vogt, Liffert ; Boekholdt, S. Matthijs ; van den Born, Bert-Jan H. ; Zwinderman, Aeilko H. ; Ferwerda, Bart ; Romman, Mohamed A.

BACKGROUND:High heritability of salt sensitivity suggests an essential role for genetics in the relationship between sodium intake and blood pressure (BP). The role of glycosaminoglycan genes, which are crucial for salinity tolerance, remains to be elucidated.METHODS:Interactions between 54 126 variants in 130 glycosaminoglycan genes and daily sodium excretion on BP were explored in 20 420 EPIC-Norfolk (European Prospective Investigation Into Cancer in Norfolk) subjects. The UK Biobank (n=414 132) and the multiethnic HELIUS study (Healthy Life in an Urban Setting; n=2239) were used for validation. Afterward, the urinary glycosaminoglycan composition was studied in HELIUS participants (n=57) stratified by genotype and upon dietary sodium loading in a time-controlled crossover intervention study (n=12).RESULTS:rs2892799 in NDST3 (heparan sulfate N-deacetylase/N-sulfotransferase 3) showed the strongest interaction with sodium on mean arterial pressure (false discovery rate 0.03), with higher mean arterial pressure for the C allele in high sodium conditions. Also, rs9654628 in HS3ST5 (heparan sulfate-glucosamine 3-sulfotransferase 5) showed an interaction with sodium on systolic BP (false discovery rate 0.03). These interactions were multiethnically validated. Stratifying for the rs2892799 genotype showed higher urinary expression of N-sulfated heparan sulfate epitope D0S0 for the T allele. Conversely, upon dietary sodium loading, urinary D0S0 expression was higher in participants with stable BP after sodium loading, and sodium-induced effects on this epitope were opposite in individuals with and without BP response to sodium.CONCLUSIONS:The C allele of rs2892799 in NDST3 exhibits higher BP in high sodium conditions when compared with low sodium conditions, whereas no differences were detected for the T allele. Concomitantly, both alleles demonstrate distinct expressions of D0S0, which, in turn, correlates with sodium-mediated BP elevation. These findings underscore the potential significance of genetic glycosaminoglycan variation in human BP regulation.

01 Jan 2022·Methods in Molecular Biology

Regulation of 3-O-Sulfation of Heparan Sulfate During Transition from the Naïve to the Primed State in Mouse Embryonic Stem Cells

Article

Author: Nishihara, Shoko ; Ota, Hayato

Mouse embryonic stem cells (mESCs), which are established from the inner cell mass of pre-implantation mouse blastocysts, rapidly expand and form dome-shaped colonies. The pluripotent state of mESCs has been defined as the "naïve" state. On the other hand, characteristics of mouse epiblast stem cells (mEpiSCs), which are derived from the epiblast of mouse post-implantation blastocysts, has been described as the "primed" state. Human embryonic stem cells/induced pluripotent stem cells (hESCs/iPSCs) are also defined as primed state cells because their gene expression pattern and signal requirement are similar to those of mEpiSCs. Both mEpiSCs and hESCs/iPSCs proliferate slowly and form flat colonies. It is therefore difficult to genetically modify primed state cells and apply them to regenerative medicine. Therefore, stable methods of reversion from the primed to the naïve state are required. Clarifying the molecular mechanisms that underpin the primed-to-naïve transition is essential for the use of such cells in basic research and regenerative medicine applications. However, this is a challenging task, since the mechanisms involved in the transition from the naïve to the primed state are still unclear. Here, we induced mEpiSC-like cells (mEpiSCLCs) from mESCs. During induction of mEpiSCLCs, we suppressed expression of 3-O-sulfated heparan sulfate (HS), the HS4C3 epitope, by shRNA-mediated knockdown of HS 3-O-sulfotransferases-5 (3OST-5, formally Hs3st5). The reduction in the level of HS 3-O-sulfation was confirmed by immunostaining with an anti-HS4C3 antibody. This protocol provides an efficient method for stable gene knockdown in mESCs and for the differentiation of mESCs to mEpiSCLCs.

17 Dec 2021·ACS CatalysisQ1 · CHEMISTRY

Structural and Substrate Specificity Analysis of 3-O-Sulfotransferase Isoform 5 to Synthesize Heparan Sulfate

Q1 · CHEMISTRY

Article

Author: Pedersen, Lars C. ; Pagadala, Vijayakanth ; Liu, Jian ; Wander, Rylee ; Xu, Yongmei ; Stancanelli, Eduardo ; Li, Jine ; Pham, Truong Quang ; Krahn, Juno M. ; Wang, Zhangjie ; Kaminski, Andrea M.

Heparan sulfate 3-O-sulfotransferase (3-OST) transfers a sulfo group to the 3-OH position of a glucosamine saccharide unit to form 3-O-sulfated heparan sulfate. 3-O-sulfation is known to be critically important for bestowing anticoagulant activity and other biological functions of heparan sulfate. Here, we report two ternary crystal structures of 3-OST-5 with PAP (3'-phosphoadenosine 5'-phosphate) and two octasaccharide substrates. We also used 3-OST-5 to synthesize six 3-O-sulfated 8-mers. Results from the structural analysis of the six 3-O-sulfated 8-mers revealed the substrate specificity of 3-OST-5. The enzyme prefers to sulfate a 6-O-sulfo glucosamine saccharide that is surrounded by glucuronic acid over a 6-O-sulfo glucosamine saccharide that is surrounded by 2-O-sulfated iduronic acid. 3-OST-5 modified 8-mers display a broad range of anti-factor Xa activity, depending on the structure of the 8-mer. We also discovered that the substrate specificity of 3-OST-5 is not governed solely by the side chains from amino acid residues in the active site. The conformational flexibility of the 2-O-sulfated iduronic acid in the saccharide substrates also contributes to the substrate specificity. These findings advance our understanding for how to control the biosynthesis of 3-O-sulfated heparan sulfate with desired biological activities.

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HS3ST5

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