4H2F

Human ecto-5'-nucleotidase (CD73): crystal form I (open) in complex with adenosine

4H2F の概要

• エントリーDOI: 10.2210/pdb4h2f/pdb
• 関連するPDBエントリー: 4H2G 4H2I 4h1y 4h2b
• 分子名称: 5'-nucleotidase, ADENOSINE, ZINC ION, ... (6 entities in total)
• 機能のキーワード: dimer, hydrolase, phosphatase, extracellular
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: P21589
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 60854.60

構造登録者

Straeter, N.,Knapp, K.M.,Zebisch, M.,Pippel, J. (登録日: 2012-09-12, 公開日: 2012-11-28, 最終更新日: 2024-11-06)

主引用文献

Knapp, K.,Zebisch, M.,Pippel, J.,El-Tayeb, A.,Muller, C.E.,Strater, N.
Crystal Structure of the Human Ecto-5'-Nucleotidase (CD73): Insights into the Regulation of Purinergic Signaling.
Structure, 20:2161-2173, 2012

PubMed Abstract: In vertebrates ecto-5'-nucleotidase (e5NT) catalyzes the hydrolysis of extracellular AMP to adenosine and represents the major control point for extracellular adenosine levels. Due to its pivotal role for activation of P1 adenosine receptors, e5NT has emerged as an appealing drug target for treatment of inflammation, chronic pain, hypoxia, and cancer. Crystal structures of the dimeric human e5NT reveal an extensive 114° conformational switch between the open and closed forms of the enzyme. The dimerization interface is formed by the C-terminal domains and exhibits interchain motions of up to 13°. Complex structures with adenosine and AMPCP indicate that structural control of the domain movement determines the selectivity for monophosphate nucleotides. Binding modes of nucleotide-derived and flavonoid-based compounds complexed to the C-terminal domain in the open form reveal an additional binding pocket of ∼210 Å(3) that might be explored to design more potent inhibitors.

PubMed: 23142347
DOI: 10.1016/j.str.2012.10.001

実験手法

X-RAY DIFFRACTION (1.85 Å)