5t05

Publication Abstract from PubMed

Heparan sulfate (HS) is a sulfated polysaccharide exhibiting essential physiological functions. HS 6-O-sulfotransferase (6-OST) transfers a sulfo group to the 6-OH position of glucosamine units to confer a variety of HS biological activities. There are three different isoforms of 6-OST in the human genome. Here, we report crystal structures of the ternary complex of 6-OST with the sulfo donor analog 3'-phosphoadenosine 5'-phosphate and three different oligosaccharide substrates at 1.95 to 2.1 A resolutions. Structural and mutational analyses reveal amino acid residues that contribute to catalysis and substrate recognition of 6-OST. Unexpectedly, the structures reveal 6-OST engages HS in a completely different orientation than other HS sulfotransferases and sheds light on the basic HS requirements for specificity. These findings also contribute structural information to understand mutations in human 6-OST isoform 1 associated with the human genetic disease idiopathic hypogonadotropic hypogonadism characterized by incomplete or lack of puberty.

Structure Based Substrate Specificity Analysis of Heparan Sulfate 6-O-Sulfotransferases.,Xu Y, Moon AF, Xu S, Krahn JM, Liu J, Pedersen LC ACS Chem Biol. 2017 Jan 20;12(1):73-82. doi: 10.1021/acschembio.6b00841. Epub, 2016 Nov 22. PMID:28103688^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.