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dc.contributor.authorMoon, Andrea F.
dc.contributor.authorXu, Yongmei
dc.contributor.authorWoody, Susan M.
dc.contributor.authorKrahn, Joseph M.
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorLiu, Jian
dc.contributor.authorPedersen, Lars C.
dc.date2012
dc.date.accessioned2022-06-27T16:06:31Z
dc.date.available2022-06-27T16:06:31Z
dc.date.issued2012-04-03
dc.identifier.citationDissecting the substrate recognition of 3-O-sulfotransferase for the biosynthesis of anticoagulant heparin, A. F. Moon, Y. Xu, S. M. Woody, J. M. Krahn, R. J. Linhardt, J. Liu, L. C. Pedersen, Proceedings of the National Academy of Sciences USA, 109, 5265–5270, 2012.
dc.identifier.issn10916490
dc.identifier.issn278424
dc.identifier.urihttps://doi.org/10.1073/pnas.1117923109
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5714
dc.descriptionProceedings of the National Academy of Sciences USA, 109, 5265–5270
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractHeparin is a polysaccharide-based natural product that is used clinically as an anticoagulant drug. Heparan sulfate 3-O-sulfotransferase (3-OST) is an enzyme that transfers a sulfo group to the 3-OH position of a glucosamine unit. 3-OST is present in multiple isoforms, and the polysaccharides modified by these different isoforms perform distinct biological functions. 3-OST isoform 1 (3-OST-1) is the key enzyme for the biosynthesis of anticoagulant heparin. Here, we report the crystal structure of the ternary complex of 3-OST-1, 3'-phosphoadenosine 5'-phosphate, and a heptasaccharide substrate. Comparisons to previously determined structures of 3-OST-3 reveal unique binding modes used by the different isoforms of 3-OST for distinguishing the fine structures of saccharide substrates. Our data demonstrate that the saccharide substrates display distinct conformations when interacting with the different 3-OST isoforms. Site-directed mutagenesis data suggest that several key amino residues, including Lys259, Thr256, and Trp283 in 3-OST-3 and Arg268 in 3-OST-1, play important roles in substrate binding and specificity between isoforms. These results deepen our understanding of the biosynthetic mechanism of heparan sulfate and provide structural information for engineering enzymes for an enhanced biosynthetic approach to heparin production.
dc.description.sponsorshipNational Institute of Environmental Health Sciences
dc.languageen_US
dc.language.isoENG
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.relation.urihttps://harc.rpi.edu/
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleDissecting the substrate recognition of 3-O-sulfotransferase for the biosynthesis of anticoagulant heparin
dc.typeArticle
dcterms.isPartOfJournal
dcterms.isVersionOfhttps://doi.org/10.1073/pnas.1117923109
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.pages5265-5270
rpi.description.volume109


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