8I1M

Crystal structure of oxidated APSK1 domain from human PAPSS1 in complex with APS and ADP

Summary for 8I1M

• Entry DOI: 10.2210/pdb8i1m/pdb
• Descriptor: PAPSS1 protein, ADENOSINE-5'-DIPHOSPHATE, ADENOSINE-5'-PHOSPHOSULFATE, ... (5 entities in total)
• Functional Keywords: 5'-phosphosulfate kinase 1, apsk1, human papss1, biosynthetic protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 23409.77

Authors

Zhang, L.,Song, W.Y.,Zhang, L. (deposition date: 2023-01-13, release date: 2023-06-28, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.699 Å)