3f5f
From Proteopedia
Crystal structure of heparan sulfate 2-O-sulfotransferase from gallus gallus as a maltose binding protein fusion.
Structural highlights
FunctionHS2ST_CHICK Catalyzes the transfer of sulfate to the C2-position of selected hexuronic acid residues within the maturing heparan sulfate (HS). 2-O-sulfation within HS, particularly of iduronate residues, is essential for HS to participate in a variety of high-affinity ligand-binding interactions and signaling processes.[1] MALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. Publication Abstract from PubMedHeparan sulfate (HS) is a polysaccharide involved in essential physiological functions from regulating cell growth to blood coagulation. HS biosynthesis involves multiple specialized sulfotransferases such as 2-O-sulfotransferase (2OST) that transfers the sulfo group to the 2-OH position of iduronic acid (IdoA) or glucuronic acid (GlcA) within HS. Here, we report the homotrimeric crystal structure of 2OST from chicken, in complex with 3'-phosphoadenosine 5'-phosphate. Structural based mutational analysis has identified amino acid residues that are responsible for substrate specificity. The mutant R189A only transferred sulfates to GlcA moieties within the polysaccharide whereas mutants Y94A and H106A preferentially transferred sulfates to IdoA units. Our results demonstrate the feasibility for manipulating the substrate specificity of 2OST to synthesize HS with unique sulfation patterns. This work will aid the development of an enzymatic approach to synthesize heparin-based therapeutics. Redirecting the substrate specificity of heparan sulfate 2-O-sulfotransferase by structurally guided mutagenesis.,Bethea HN, Xu D, Liu J, Pedersen LC Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18724-9. Epub 2008 Nov 20. PMID:19022906[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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