THE STRUCTURE OF A COMPLEX OF RECOMBINANT HIRUDIN AND HUMAN ALPHA-THROMBIN
THE STRUCTURE OF A COMPLEX OF RECOMBINANT HIRUDIN AND HUMAN ALPHA-THROMBIN
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DOI：
10.1126/science.2374926
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发表时间：
1990-07-20
期刊：
影响因子：
56.9
通讯作者：
FENTON, JW
中科院分区：
文献类型：
--
作者：
RYDEL, TJ;RAVICHANDRAN, KG;FENTON, JW
重组水飞蓟素-凝血酶复合体的晶体结构在2.3埃(？)决议。水飞蓟素由一个NH2末端的球形结构域和一个长的(39.ANG.)COOH-末端扩展结构域。水飞蓟素的Ile1到Tyr3残基与凝血酶的Ser214到Glu217形成平行的β-链，Ile1的氮原子与Ser195γ形成氢键。催化部位的原子，但凝血酶的特异性口袋不参与相互作用。COOH末端片段与凝血酶的阴离子结合外切点进行了大量的静电相互作用，而最后五个残基处于螺旋环中，形成了许多疏水接触。总而言之，水飞蓟素的65个残基中有27个与凝血酶的接触小于4.0 ng(10个离子对和23个氢苯键)。这种丰富的相互作用可能是水飞蓟素高亲和力和特异性的原因。
The crytstallographic structure of recombinant hirudin-thrombin complex has been solved at 2.3 angstrom (.ANG.) resolution. Hirudin consists of an NH2-terminal globular domain and a long (39 .ANG.) COOH-terminal extended domain. Residues Ile1 to Tyr3 of hirudin form a parallel .beta.-strand with Ser214 to Glu217 of thrombin with the nitrogen atom of Ile1 making a hydrogen bond with ser195 O.gamma. atom of the catalytic site, but the specificity pocket of thrombin is not involved in the interaction. The COOH-terminal segment makes numerous electrostatic interactions with an anion-binding exosite of thrombin, whereas the last five residues are in a helical loop that forms many hydrophobic contacts. In all, 27 of the 65 residues of hirudin have contacts less than 4.0 .ANG. with thrombin (10 ion pairs and 23 hydroben bonds). Such abundant interaction may account for the high affinity and specificity of hirudin.