3F5F

Crystal structure of heparan sulfate 2-O-sulfotransferase from gallus gallus as a maltose binding protein fusion.

3F5F の概要

• エントリーDOI: 10.2210/pdb3f5f/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: Maltose-binding periplasmic protein, Heparan sulfate 2-O-sulfotransferase 1, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ADENOSINE-3'-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: maltose binding protein, fusion, heparan sulfate biosynthesis, sulfotransferase, glycoprotein, golgi apparatus, membrane, signal-anchor, transferase, transmembrane, periplasm, sugar transport, transport
• 由来する生物種: Escherichia coli K-12 (bantam,chickens); 詳細
• 細胞内の位置: Golgi apparatus membrane ; Single-pass type II membrane protein : Q76KB1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 75055.83

構造登録者

Bethea, H.N.,Xu, D.,Liu, J.,Pedersen, L.C. (登録日: 2008-11-03, 公開日: 2008-12-16, 最終更新日: 2024-10-16)

主引用文献

Bethea, H.N.,Xu, D.,Liu, J.,Pedersen, L.C.
Redirecting the substrate specificity of heparan sulfate 2-O-sulfotransferase by structurally guided mutagenesis.
Proc.Natl.Acad.Sci.USA, 105:18724-18729, 2008

PubMed Abstract: Heparan 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.

PubMed: 19022906
DOI: 10.1073/pnas.0806975105

実験手法

X-RAY DIFFRACTION (2.65 Å)