The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle 4.
The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle 4.
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DOI：
10.1021/bi00107a030
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发表时间：
1991-10
期刊：
影响因子：
2.9
通讯作者：
T. Wu;K. Padmanabhan;A. Tulinsky;A. Mulichak
中科院分区：
文献类型：
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作者：
T. Wu;K. Padmanabhan;A. Tulinsky;A. Mulichak
纤溶酶原kringle 4-ε-氨基己酸（ACA）复合物（K4-ACA）的晶体结构已经通过分子置换旋转-平移方法利用精制的apo-K4结构作为搜索模型来求解（Mulichak等人，1991），并且在2.25-A分辨率下，其已被改进为R值为0.148。K4-ACA结构由两个kringle残基，kringle沿着ACA配体和106个水分子组成。赖氨酸结合位点已被证实是一个相对开放和浅的凹陷，内衬的芳环的Trp62，Phe64，和Trp72，这提供了一个高度非极性的环境之间的双电荷的阴离子和阳离子中心形成的Asp55/Asp57和Lys35/Arg71。两性离子ACA配体分子通过氢键离子对相互作用和带电中心之间的货车范德华接触保持。比较了apo-K4和K4-ACA的赖氨酸结合位点：主链和侧链位置的rms差异分别为0.25和0.69 A，两者实际上都在测定误差范围内。结合位点的最大偏差是由于不同的晶体堆积相互作用。因此，赖氨酸结合位点似乎是预先形成的，并且赖氨酸结合不需要宿主的构象变化。赖氨酸与K4结合的NMR研究结果与K4-ACA的结构相关，并且吻合得很好。
The crystallographic structure of the plasminogen kringle 4-epsilon-aminocaproic acid (ACA) complex (K4-ACA) has been solved by molecular replacement rotation-translation methods utilizing the refined apo-K4 structure as a search model (Mulichak et al., 1991), and it has been refined to an R value of 0.148 at 2.25-A resolution. The K4-ACA structure consists of two interkringle residues, the kringle along with the ACA ligand, and 106 water molecules. The lysine-binding site has been confirmed to be a relatively open and shallow depression, lined by aromatic rings of Trp62, Phe64, and Trp72, which provide a highly nonpolar environment between doubly charged anionic and cationic centers formed by Asp55/Asp57 and Lys35/Arg71. A zwitterionic ACA ligand molecule is held by hydrogen-bonded ion pair interactions and van der Waals contacts between the charged centers. The lysine-binding site of apo-K4 and K4-ACA have been compared: the rms differences in main-chain and side-chain positions are 0.25 and 0.69 A, respectively, both practically within error of the determinations. The largest deviations in the binding site are due to different crystal packing interactions. Thus, the lysine-binding site appears to be preformed, and lysine binding does not require conformational changes of the host. The results of NMR studies of lysine binding with K4 are correlated with the structure of K4-ACA and agree well.