1XSC

Structure of the nudix enzyme AP4A hydrolase from homo sapiens (E63A mutant) in complex with ATP

1XSC の概要

• エントリーDOI: 10.2210/pdb1xsc/pdb
• 関連するPDBエントリー: 1XSA 1XSB
• NMR情報: BMRB: 6336
• 分子名称: Bis(5'-nucleosyl)-tetraphosphatase, ADENOSINE-5'-TRIPHOSPHATE (2 entities in total)
• 機能のキーワード: nudix enzyme, human ap4a atp hydrolase, alpha-beta, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17824.99

構造登録者

Swarbrick, J.D.,Buyya, S.,Gunawardana, D.,Gayler, K.R.,McLennan, A.G.,Gooley, P.R. (登録日: 2004-10-18, 公開日: 2004-12-21, 最終更新日: 2024-05-29)

主引用文献

Swarbrick, J.D.,Buyya, S.,Gunawardana, D.,Gayler, K.R.,McLennan, A.G.,Gooley, P.R.
Structure and Substrate-binding Mechanism of Human Ap4A Hydrolase
J.Biol.Chem., 280:8471-8481, 2005

PubMed Abstract: Asymmetric diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) hydrolases play a major role in maintaining homeostasis by cleaving the metabolite diadenosine tetraphosphate (Ap(4)A) back into ATP and AMP. The NMR solution structures of the 17-kDa human asymmetric Ap(4)A hydrolase have been solved in both the presence and absence of the product ATP. The adenine moiety of the nucleotide predominantly binds in a ring stacking arrangement equivalent to that observed in the x-ray structure of the homologue from Caenorhabditis elegans. The binding site is, however, markedly divergent to that observed in the plant/pathogenic bacteria class of enzymes, opening avenues for the exploration of specific therapeutics. Binding of ATP induces substantial conformational and dynamic changes that were not observed in the C. elegans structure. In contrast to the C. elegans homologue, important side chains that play a major role in substrate binding do not have to reorient to accommodate the ligand. This may have important implications in the mechanism of substrate recognition in this class of enzymes.

PubMed: 15596429
DOI: 10.1074/jbc.M412318200

実験手法

SOLUTION NMR