We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

8i1m

From Proteopedia

Jump to: navigation, search

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

Structural highlights

8i1m is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.699Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PAPS1_HUMAN Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate-activation pathway. Also involved in the biosynthesis of sulfated L-selectin ligands in endothelial cells.

Publication Abstract from PubMed

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.

Redox switching mechanism of the adenosine 5'-phosphosulfate kinase domain (APSK2) of human PAPS synthase 2.,Zhang L, Song W, Li T, Mu Y, Zhang P, Hu J, Lin H, Zhang J, Gao H, Zhang L Structure. 2023 Jul 6;31(7):826-835.e3. doi: 10.1016/j.str.2023.04.012. Epub 2023 , May 18. PMID:37207644^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. 2023 May 10:S0969-2126(23)00135-1. PMID:37207644 doi:10.1016/j.str.2023.04.012