Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.
Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.
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人类 NUDT5 的晶体结构揭示了底物特异性的结构基础。
DOI：
10.1016/j.jmb.2006.09.078
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发表时间：
2006
影响因子：
5.6
通讯作者：
Jianping Ding
中科院分区：
文献类型：
--
作者：
M. Zha;C. Zhong;Yingjie Peng;Hongyu Hu;Jianping Ding
人NUDT5(HNUDT5)是一种属于Nudex水解酶超家族的ADP核糖焦磷酸酶(ADPRase)。它通过将ADP-核糖(ADPR)水解为AMP和5‘-磷酸核糖，在控制细胞内ADPR水平，防止非酶ADP-核糖化方面发挥重要作用。本文报道了hNUDT5的载脂蛋白形式、与ADPR的络合物以及与AMP与结合的镁离子的络合物的晶体结构。HNUDT5形成具有实质性结构域交换的同源二聚体，并且呈现出比人ADPRase NUDT9更类似于大肠杆菌ADPRase ORF209的结构。底物的腺嘌呤部分是通过碱基N1和N6与一个亚基的Glu47之间以及碱基的N7和另一个亚基的Arg51之间的氢键作用而被酶特异性识别的，这为hNUDT5对ADP-糖的高选择性提供了分子基础。与大肠杆菌ADPRase ORF209和ADPXase ORF186的结构比较表明，ORF186中L8环上的芳香族残基的存在似乎与其在ApNA上的酶活性呈正相关，而hNUDT5和ORF209不含芳香族残基，因此在ApNA上活性较低或没有。
Human NUDT5 (hNUDT5) is an ADP-ribose pyrophosphatase (ADPRase) belonging to the Nudix hydrolase superfamily. It presumably plays important roles in controlling the intracellular level of ADP-ribose (ADPR) to prevent non-enzymatic ADP-ribosylation by hydrolyzing ADPR to AMP and ribose 5′-phosphate. We report here the crystal structures of hNUDT5 in apo form, in complex with ADPR, and in complex with AMP with bound Mg2+. hNUDT5 forms a homodimer with substantial domain swapping and assumes a structure more similar to Escherichia coli ADPRase ORF209 than human ADPRase NUDT9. The adenine moiety of the substrates is specifically recognized by the enzyme via hydrogen-bonding interactions between N1 and N6 of the base and Glu47 of one subunit, and between N7 of the base and Arg51 of the other subunit, providing the molecular basis for the high selectivity of hNUDT5 for ADP-sugars over other sugar nucleotides. Structural comparisons with E. coli ADPRase ORF209 and ADPXase ORF186 indicate that the existence of an aromatic residue on loop L8 in ORF186 seems to be positively correlated with its enzymatic activity on APnA, whereas hNUDT5 and ORF209 contain no such residue and thus have low or no activities on APnA.
影响因子：
5.6
作者：
Shen, BW;Perraud, AL;Stoddard, BL
通讯作者：
Stoddard, BL
来自耐辐射奇球菌的 Nudix 水解酶 DR1025 及其配体复合物的结构研究。
DOI：
10.1016/j.jmb.2004.01.065
发表时间：
2004
期刊：
Journal of molecular biology.
影响因子：
--
作者：
Ranatunga,Wasantha;Hill,EmmaE;Mooster,JanaL;Holbrook,ElizabethL;Schulze-Gahmen,Ursula;Xu,WenLian;Bessman,MauriceJ;Brenner,StevenE;Holbrook,StephenR
通讯作者：
Holbrook,StephenR