2HGT

STRUCTURE OF THE HIRUGEN AND HIRULOG 1 COMPLEXES OF ALPHA-THROMBIN

2HGT の概要

• エントリーDOI: 10.2210/pdb2hgt/pdb
• 関連するBIRD辞書のPRD_ID: PRD_001145 PRD_001148
• 分子名称: ALPHA-THROMBIN (SMALL SUBUNIT), ALPHA-THROMBIN (LARGE SUBUNIT), Hirulog, ... (5 entities in total)
• 機能のキーワード: hydrolase(serine protease), hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734; Secreted: P28504
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 36076.06

構造登録者

Tulinsky, A.,Carperos, V. (登録日: 1991-06-03, 公開日: 1994-01-31, 最終更新日: 2024-10-30)

主引用文献

Skrzypczak-Jankun, E.,Carperos, V.E.,Ravichandran, K.G.,Tulinsky, A.,Westbrook, M.,Maraganore, J.M.
Structure of the hirugen and hirulog 1 complexes of alpha-thrombin.
J.Mol.Biol., 221:1379-1393, 1991

PubMed Abstract: The isomorphous structures of the hirugen (N-acetylhirudin 53'-64' with sulfato-Tyr63') and hirulog 1 (D-Phe-Pro-Arg-Pro-(Gly)4 desulfato-Tyr63'-hirugen) complexes of human alpha-thrombin have been determined and refined at 2.2 A resolution to crystallographic R-factors of 0.167 and 0.163, respectively. The binding of hirugen to thrombin is similar to that of the binding of the C-terminal dodecapeptide of hirudin, including that of the terminal 3(10) helical turn. The sulfato Tyr63', which, as a result of sulfation, increases the binding affinity by an order of magnitude, is involved in an extended hydrogen bonding network utilizing all three sulfato oxygen atoms. The hirugen-thrombin complex is the first thrombin structure determined to have an unobstructed active site; this site is practically identical in positioning of catalytic residues and in its hydrogen bonding pattern with that of other serine proteinases. Hirulog 1, which is a poor thrombin substrate, is cleaved at the Arg3'-Pro4' bond in the crystal structure. The Arg3' of hirulog 1 occupies the specificity site, the D-Phe-Pro-Arg tripeptide is positioned like that of D-Phe-Pro-Arg chloromethylketone in the active site and the Pro4'(Gly)4 spacer to hirugen is disordered in the structure, as is the 3(10) turn of hirugen. The latter must be related to the simultaneous absence both of sulfation and of the last residue of hirudin (Gln65'). In addition, the autolysis loop of thrombin (Lys145-Gly150) is disordered in both structures. Changes in circular dichroism upon hirugen binding are therefore most likely the result of the flexibility associated with this loop.

PubMed: 1942057
DOI: 10.1016/0022-2836(91)80132-E

実験手法

X-RAY DIFFRACTION (2.2 Å)