Deciphering the substrate recognition mechanisms of the heparan sulfate 3- O -sulfotransferase-3
Year: 2021
Type: article
Abstract: -sulfated octasaccharide (8-mer 3). The 8-mer 1 is a known favorable substrate for 3-OST-3, whereas the 8-mer 3 is an unfavorable one. Unlike the 8-mer 1, we discovered that the 8-mer 3 displays two binding orientations to the enzyme: productive binding and non-productive binding. Results from the enzyme activity studies demonstrate that 8-mer 3 can contribute to either substrate or product inhibition, possibly attributed to a non-productive binding mode. Our results suggest that heparan sulfate substrates interact with the 3-OST-3 enzyme in more than one orientation, which may regulate the activity of the enzyme. Our findings also suggest that different binding orientations between polysaccharides and their protein binding partners could influence biological outcomes.
Source: RSC Chemical Biology
DOI: 10.1039/d1cb00079a
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,962
Awards: G1039801292, Diverse Heparan Sulfate Oligosaccharide Libraries For Understanding and Therapeutically Manipulating Glycosaminoglycans, Quantitative analysis of heparan sulfate using 13C-labeled standards, G678799539, G9000099027, G9000177019, G9000233146, G9000326484, G9000331503, Development of dekaparin to replace animal-sourced heparin
OpenAlex ID: W3171487399