7FHA

Crystal structure of the ATP sulfurylase domain of human PAPSS2 in complex with APS

7FHA の概要

• エントリーDOI: 10.2210/pdb7fha/pdb
• 分子名称: Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2, ADENOSINE-5'-PHOSPHOSULFATE, beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: atp sulfurylase, biosynthetic protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91522.79

構造登録者

Zhang, P.,Zhang, L.,Zhang, L. (登録日: 2021-07-29, 公開日: 2021-12-01, 最終更新日: 2023-11-29)

主引用文献

Zhang, P.,Zhang, L.,Hou, Z.,Lin, H.,Gao, H.,Zhang, L.
Structural basis for the substrate recognition mechanism of ATP-sulfurylase domain of human PAPS synthase 2.
Biochem.Biophys.Res.Commun., 586:1-7, 2022

PubMed Abstract: Sulfation is an essential modification on biomolecules in living cells, and 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) is its unique and universal sulfate donor. Human PAPS synthases (PAPSS1 and 2) are the only enzymes that catalyze PAPS production from inorganic sulfate. Unexpectedly, PAPSS1 and PAPSS2 do not functional complement with each other, and abnormal function of PAPSS2 but not PAPSS1 leads to numerous human diseases including bone development diseases, hormone disorder and cancers. Here, we reported the crystal structures of ATP-sulfurylase domain of human PAPSS2 (ATPS2) and ATPS2 in complex with is product 5'-phosphosulfate (APS). We demonstrated that ATPS2 recognizes the substrates by using family conserved residues located on the HXXH and PP motifs, and achieves substrate binding and releasing by employing a non-conserved phenylalanine (Phe550) through a never observed flipping mechanism. Our discovery provides additional information to better understand the biological function of PAPSS2 especially in tumorigenesis, and may facilitate the drug discovery against this enzyme.

PubMed: 34818583
DOI: 10.1016/j.bbrc.2021.11.062

実験手法

X-RAY DIFFRACTION (2 Å)