2OCV
Structural basis of Na+ activation mimicry in murine thrombin
2OCV の概要
エントリーDOI | 10.2210/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: 17428793DOI: 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) |
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