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2OCV

Structural basis of Na+ activation mimicry in murine thrombin

2OCV の概要
エントリーDOI10.2210/pdb2ocv/pdb
関連するPDBエントリー1SHH
分子名称Thrombin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
機能のキーワードserine protease, hydrolase
由来する生物種Mus musculus (house mouse)
詳細
タンパク質・核酸の鎖数2
化学式量合計36141.26
構造登録者
Marino, F.,Chen, Z.,Ergenekan, C.E.,Bush, L.A.,Mathews, F.S.,Di Cera, E. (登録日: 2006-12-21, 公開日: 2007-04-10, 最終更新日: 2024-12-25)
主引用文献Marino, F.,Chen, Z.W.,Ergenekan, C.E.,Bush-Pelc, L.A.,Mathews, F.S.,Di Cera, E.
Structural basis of na+ activation mimicry in murine thrombin.
J.Biol.Chem., 282:16355-16361, 2007
Cited by
PubMed Abstract: Unlike human thrombin, murine thrombin lacks Na+ activation due to the charge reversal substitution D222K in the Na+ binding loop. However, the enzyme is functionally stabilized in a Na+-bound form and is highly active toward physiologic substrates. The structural basis of this peculiar property is unknown. Here, we present the 2.2 A resolution x-ray crystal structure of murine thrombin in the absence of inhibitors and salts. The enzyme assumes an active conformation, with Ser-195, Glu-192, and Asp-189 oriented as in the Na+-bound fast form of human thrombin. Lys-222 completely occludes the pore of entry to the Na+ binding site and positions its side chain inside the pore, with the Nzeta atom H-bonded to the backbone oxygen atoms of Lys-185, Asp-186b, and Lys-186d. The same architecture is observed in the 1.75 A resolution structure of a thrombin chimera in which the human enzyme carries all residues defining the Na+ pore in the murine enzyme. These findings demonstrate that Na+ activation in thrombin is linked to the architecture of the Na+ pore. The molecular strategy of Na+ activation mimicry unraveled for murine thrombin is relevant to serine proteases and enzymes activated by monovalent cations in general.
PubMed: 17428793
DOI: 10.1074/jbc.M701323200
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (2.2 Å)
構造検証レポート
Validation report summary of 2ocv
検証レポート(詳細版)ダウンロードをダウンロード

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件を2025-07-23に公開中

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