2PEY

Crystal structure of deletion mutant of APS-kinase domain of human PAPS-synthetase 1

Summary for 2PEY

• Entry DOI: 10.2210/pdb2pey/pdb
• Related: 2pez
• Descriptor: Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPS synthetase 1) (PAPSS 1) (Sulfurylase kinase 1) (SK1) (SK 1), ADENOSINE-5'-PHOSPHOSULFATE, 2'-DEOXYADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: protein-nucleic acid complex, nmp-kinase fold, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 40998.63

Authors

Sekulic, N.,Lavie, A. (deposition date: 2007-04-03, release date: 2007-05-29, Last modification date: 2023-08-30)

Primary citation

Sekulic, N.,Konrad, M.,Lavie, A.
Structural mechanism for substrate inhibition of the adenosine 5'-phosphosulfate kinase domain of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 and its ramifications for enzyme regulation.
J.Biol.Chem., 282:22112-22121, 2007

PubMed Abstract: In mammals, the universal sulfuryl group donor molecule 3'-phosphoadenosine 5'-phosphosulfate (PAPS) is synthesized in two steps by a bifunctional enzyme called PAPS synthetase. The APS kinase domain of PAPS synthetase catalyzes the second step in which APS, the product of the ATP-sulfurylase domain, is phosphorylated on its 3'-hydroxyl group to yield PAPS. The substrate APS acts as a strong uncompetitive inhibitor of the APS kinase reaction. We generated truncated and point mutants of the APS kinase domain that are active but devoid of substrate inhibition. Structural analysis of these mutant enzymes reveals the intrasubunit rearrangements that occur upon substrate binding. We also observe intersubunit rearrangements in this dimeric enzyme that result in asymmetry between the two monomers. Our work elucidates the structural elements required for the ability of the substrate APS to inhibit the reaction at micromolar concentrations. Because the ATP-sulfurylase domain of PAPS synthetase influences these elements in the APS kinase domain, we propose that this could be a communication mechanism between the two domains of the bifunctional enzyme.

PubMed: 17540769
DOI: 10.1074/jbc.M701713200

Experimental method

X-RAY DIFFRACTION (1.88 Å)