8I1O

Crystal structure of APSK2 domain from human PAPSS2 in complex with exogenous APS and ADP

8I1O の概要

• エントリーDOI: 10.2210/pdb8i1o/pdb
• 分子名称: Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE-5'-PHOSPHOSULFATE, ... (4 entities in total)
• 機能のキーワード: 5'-phosphosulfate kinase 2 domain, apsk2, human papss2, biosynthetic protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93475.74

構造登録者

Zhang, L.,Song, W.Y.,Zhang, L. (登録日: 2023-01-13, 公開日: 2023-06-28, 最終更新日: 2024-05-29)

主引用文献

Zhang, L.,Song, W.,Li, T.,Mu, Y.,Zhang, P.,Hu, J.,Lin, H.,Zhang, J.,Gao, H.,Zhang, L.
Redox switching mechanism of the adenosine 5'-phosphosulfate kinase domain (APSK2) of human PAPS synthase 2.
Structure, 31:826-835.e3, 2023

PubMed Abstract: Adenosine 5'-phosphosulfate kinase (APSK) catalyzes the rate-limiting biosynthetic step of the universal sulfuryl donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS). In higher eukaryotes, the APSK and ATP sulfurylase (ATPS) domains are fused in a single chain. Humans have two bifunctional PAPS synthetase isoforms: PAPSS1 with the APSK1 domain and PAPSS2 containing the APSK2 domain. APSK2 displays a distinct higher activity for PAPSS2-mediated PAPS biosynthesis during tumorigenesis. How APSK2 achieves excess PAPS production has remained unclear. APSK1 and APSK2 lack the conventional redox-regulatory element present in plant PAPSS homologs. Here we elucidate the dynamic substrate recognition mechanism of APSK2. We discover that APSK1 contains a species-specific Cys-Cys redox-regulatory element that APSK2 lacks. The absence of this element in APSK2 enhances its enzymatic activity for excess PAPS production and promotes cancer development. Our results help to understand the roles of human PAPSSs during cell development and may facilitate PAPSS2-specific drug discovery.

PubMed: 37207644
DOI: 10.1016/j.str.2023.04.012

実験手法

X-RAY DIFFRACTION (2.4 Å)