Crystal structure of human micro-crystallin complexed with NADPH.
Crystal structure of human micro-crystallin complexed with NADPH.
复制标题
与 NADPH 复合的人微晶状体蛋白的晶体结构。
DOI：
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
W. Gong
中科院分区：
文献类型：
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作者：
Zhongjun Cheng;Lihua（孙丽华） Sun;Jianhua He;W. Gong
人胞浆3,5,3′-三碘- l -甲状腺原氨酸结合蛋白，又称mu-crystallin或CRYM，在将3,5,3′-三碘- l -甲状腺原氨酸（T(3)）转运到细胞核中，调节甲状腺激素相关基因的表达中起着重要的生理作用。人类CRYM的细菌同源物恶臭假单胞菌鸟氨酸环脱氨酶和黄腐古舌菌丙氨酸脱氢酶的晶体结构已经得到，但CRYM的结构尚未见报道。在这里，我们报道了人类CRYM与NADPH结合的晶体结构细化到2.6 A，并且在不对称单元中有一个二聚体。该结构包含两个结构域：一个Rossmann折叠样nadph结合结构域和一个二聚化结构域。在同一不对称单元的两种人CRYM单体中观察到Arg83-His92环的不同构象。Val89-Pro90的肽键在一个单体上是反式构型，而在另一个单体上是顺式构型。对人类微晶蛋白的结构与其结构特征的同源物进行了详细的比较，包括总体比较和活性位点的叠加。最后，通过与结构同源物的比较，提出了人类CRYM中一个假定的T(3)结合位点。
Human cytosolic 3,5,3'-triiodo-L-thyronine-binding protein, also called mu-crystallin or CRYM, plays important physiological roles in transporting 3,5,3'-triiodo-L-thyronine (T(3)) into nuclei and regulating thyroid-hormone-related gene expression. The crystal structure of human CRYM's bacterial homolog Pseudomonas putida ornithine cyclodeaminase and Archaeoglobus fulgidus alanine dehydrogenase have been available, but no CRYM structure has been reported. Here, we report the crystal structure of human CRYM bound with NADPH refined to 2.6 A, and there is one dimer in the asymmetric unit. The structure contains two domains: a Rossmann fold-like NADPH-binding domain and a dimerization domain. Different conformations of the loop Arg83-His92 have been observed in two monomers of human CRYM in the same asymmetric unit. The peptide bond of Val89-Pro90 is a trans-configuration in one monomer but a cis-configuration in the other. A detailed comparison of the human mu-crystallin structure with its structurally characterized homologs including the overall comparison and superposition of active sites was conducted. Finally, a putative T(3)-binding site in human CRYM is proposed based on comparison with structural homologs.