Mather T, Oganessyan V, Hof P, Huber R, Foundling S, Esmon C, Bode W
Abteilung Strukturforschung, Max Planck Institut für Biochemie, Martinsried, Germany.
EMBO J. 1996 Dec 16;15(24):6822-31.
The structure of the Gla-domainless form of the human anticoagulant enzyme activated protein C has been solved at 2.8 A resolution. The light chain is composed of two domains: an epidermal growth factor (EGF)-like domain modified by a large insert containing an additional disulfide, followed by a typical EGF-like domain. The arrangement of the long axis of these domains describes an angle of approximately 80 degrees. Disulfide linked to the light chain is the catalytic domain, which is generally trypsin-like but contains a large insertion loop at the edge of the active site, a third helical segment, a prominent cationic patch analogous to the anion binding exosite I of thrombin and a trypsin-like Ca[II] binding site. The arrangement of loops around the active site partially restricts access to the cleft. The S2 and S4 subsites are much more polar than in factor Xa and thrombin, and the S2 site is unrestricted. While quite open and exposed, the active site contains a prominent groove, the surface of which is very polar with evidence for binding sites on the primed side, in addition to those typical of the trypsin class found on the non-primed side.
人抗凝酶活化蛋白C无γ-羧基谷氨酸（Gla）结构域形式的结构已在2.8埃分辨率下解析出来。轻链由两个结构域组成：一个表皮生长因子（EGF）样结构域，被一个含有额外二硫键的大插入片段修饰，接着是一个典型的EGF样结构域。这些结构域长轴的排列形成约80度的夹角。与轻链相连的二硫键部分是催化结构域，其总体上类似胰蛋白酶，但在活性位点边缘含有一个大的插入环、一个第三螺旋片段、一个类似于凝血酶阴离子结合外位点I的突出阳离子斑块以及一个胰蛋白酶样的Ca[II]结合位点。活性位点周围环的排列部分限制了对裂隙的 access。S2和S4亚位点比因子Xa和凝血酶中的极性大得多，且S2位点无限制。虽然活性位点相当开放且暴露，但它含有一个突出的凹槽，其表面极性很强，除了在非引发侧发现的那些典型的胰蛋白酶类结合位点外，在引发侧也有结合位点的证据。
