NAD-binding mode and the significance of intersubunit contact revealed by the crystal structure of Mycobacterium tuberculosis NAD kinase-NAD complex
NAD-binding mode and the significance of intersubunit contact revealed by the crystal structure of Mycobacterium tuberculosis NAD kinase-NAD complex
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DOI：
10.1016/j.bbrc.2004.11.163
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发表时间：
2005-02-11
影响因子：
3.1
通讯作者：
Murata, K
中科院分区：
文献类型：
--
作者：
Mori, S;Yamasaki, M;Murata, K
NAD激酶是NADP生物合成的关键酶。在2.6埃分辨率下，我们计算了结核分枝杆菌多聚磷酸/三磷酸腺苷-NAD酶(Ppnk)与NAD(Ppnk-NAD)的络合物(Ppnk-NAD)的晶体结构，揭示了结构和NAD结合的细节。Apo-Ppnk和Ppnk-NAD的三级结构的叠加在一个环(Ppnk-柔性环)中显示出显著的构象差异。作为一种四元结构，这些Ppnk结构在溶液中表现为四聚体。值得注意的是，Ppnk-灵活环参与了亚基间的接触，并可能与另一个亚基的NAD结合有关。此外，这两个残基(Asp189，His226)大大有助于在另一个亚基上创建NAD结合位点。这两个残基和参与NAD结合的残基是保守的。然而，与Ppnk-柔性环相对应的残基不是保守的，这使我们推测Ppnk-柔性环可能是Ppnk特异的。(C)2004 Elsevier Inc.保留所有权利。
NAD kinase is a key enzyme in NADP biosynthesis. We solved the crystal structure of polyphosphate/ATP-NAD kinase from Mycobacterium tuberculosis (Ppnk) complexed with NAD (Ppnk-NAD) at 2.6 Angstrom resolution using apo-Ppnk structure solved in this work, and revealed the details of the structure and NAD-binding site. Superimposition of tertiary structures of apo-Ppnk and Ppnk-NAD demonstrated a substantial conformational difference in a loop (Ppnk-flexible loop). As a quaternary structure, these Ppnk structures exhibited tetramer as in solution condition. Notably, the Ppnk-flexible loop was involved in the intersubunit contact and probably related to the NAD-binding of the other subunit. Furthermore, the two residues (Asp189, His226) substantially contributed to creating NAD-binding site on the other subunit. The two residues and the residues involved in NAD-binding were conserved. However, residues corresponding to the Ppnk-flexible loop were not conserved, making us to speculate that the Ppnk-flexible loop may be Ppnk-specific. (C) 2004 Elsevier Inc. All rights reserved.