2PEZ

Crystal structrue of deletion mutant of APS-kinase domain of human PAPS-synthetase 1 in complex with cyclic PAPS and dADP

2PEZ の概要

• エントリーDOI: 10.2210/pdb2pez/pdb
• 関連するPDBエントリー: 2PEY
• 分子名称: Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPS synthetase 1) (PAPSS 1) (Sulfurylase kinase 1) (SK1) (SK 1), (2S,3AR,4R,6R,6AR)-4-(6-AMINO-9H-PURIN-9-YL)-6-({[(R)-HYDROXY(SULFOOXY)PHOSPHORYL]OXY}METHYL)TETRAHYDROFURO[3,4-D][1,3,2]DIOXAPHOSPHOL-2-OL 2-OXIDE, 2'-DEOXYADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: nmp-kinase fold, protein in complex with nucleic acid, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41060.59

構造登録者

Sekulic, N.,Lavie, A. (登録日: 2007-04-03, 公開日: 2007-05-29, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.4 Å)