7FHA

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

Summary for 7FHA

• Entry DOI: 10.2210/pdb7fha/pdb
• Descriptor: Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2, ADENOSINE-5'-PHOSPHOSULFATE, beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: atp sulfurylase, biosynthetic protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 91522.79

Authors

Zhang, P.,Zhang, L.,Zhang, L. (deposition date: 2021-07-29, release date: 2021-12-01, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)