Heparan sulfate glucosamine 3-O-sulfotransferase 4 (HS3ST4)

Heparan sulfate glucosamine 3-O-sulfotransferase 4 (HS3ST4) is an enzyme that catalyzes the transfer of a sulfo group to the 3-O position of glucosamine residues in heparan sulfate. This rare modification creates specific motifs required for interactions with proteins such as antithrombin (affecting blood coagulation) and viral proteins (notably, it facilitates the entry of herpes simplex virus type 1 through modified cell surface heparan sulfate). HS3ST4 is part of a multigene sulfotransferase family, is particularly expressed in brain tissues, and is implicated in both physiological processes (e.g., neural regulation) and pathologies such as cancer and viral infection. Targeting its activity or the resultant sulfated HS motifs may have therapeutic potential for anticoagulation and antiviral strategies, but also presents challenges due to the enzyme’s diverse and tissue-specific functions[1][2][3][4][5][7].

Other names

3-OST-43OST4HS3ST430ST4h3-OST-4Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 4Heparan sulfate (glucosamine) 3-O-sulfotransferase 4Heparan sulfate 3-O-sulfotransferase 4

Not directly targeted by current approved drugs. Potential mechanism: Modulation of heparan sulfate structure to influence anticoagulant activity and reduce platelet factor 4 binding (and thus potentially reduce heparin-induced thrombocytopenia)[2]. Facilitates protein-protein interactions via generation of specific sulfation motifs (e.g., HS-antithrombin, HS-glycoprotein D for HSV-1)[4][5]