2.6 A X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase .
2.6 A X-ray crystal structure of human p53R2, a p53-inducible ribonucleotide reductase .
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2.6 人 p53R2（一种 p53 诱导型核糖核苷酸还原酶）的 X 射线晶体结构。
DOI：
10.1021/bi9001425
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发表时间：
2009-11-24
期刊：
影响因子：
2.9
通讯作者：
Yen, Yun
中科院分区：
文献类型：
--
作者：
Smith, Peter;Zhou, Bingsen;Ho, Nam;Yuan, Yate-Ching;Su, Leila;Tsai, Shiou-Chuan;Yen, Yun
人p53 R2（hp 53 R2）是一个由351个残基组成的p53诱导型核糖核苷酸还原酶（RNR）小亚基。它与hRRM 2共享>80%的序列同一性，hRRM 2是负责DNA复制所用脱氧核糖核苷酸（dNTP）库的正常维持的小RNR亚基，其在S期以细胞周期依赖性方式具有活性。但hp 53 R2不是环状dNTP合成，而是以p53依赖的方式为G 0-G1期细胞的DNA修复提供dNTP。hp 53 R2的第一个X射线晶体结构解析为2.6 μ m，其中单体A和B分别表现出单核和双核铁占据。hp 53 R2和hRRM 2之间三个区域的显著结构差异突出了铁同化中可能的调节作用，并有助于解释先前观察到的自由基铁中心的流动性和可及性的物理和生化差异，以及两种酶之间的自由基转移途径。首次揭示了hp 53 R2和hRRM 2的序列-结构-功能相关性。从结构工作中获得的见解将用于鉴定RNR小亚基的生物学功能，调节机制和抑制剂的选择。
Human p53R2 (hp53R2) is a 351 residue p53-inducible ribonucleotide reductase (RNR) small subunit. It shares >80% sequence identity with hRRM2, the small RNR subunit responsible for normal maintenance of the deoxyribonucleotide (dNTP) pool used for DNA replication, which is active during the S-phase in a cell-cycle dependent fashion. But rather than cyclic dNTP synthesis, hp53R2 has been shown to supply dNTPs for DNA repair to cells in G0-G1 in a p53-dependent fashion. The first x-ray crystal structure of hp53R2 is solved to 2.6 Å, in which monomers A and B exhibit mono- and bi-nuclear iron occupancy, respectively. The pronounced structural differences at three regions between hp53R2 and hRRM2 highlight the possible regulatory role in iron assimilation, and help explain previously observed physical and biochemical differences in the mobility and accessibility of the radical-iron center, as well as radical transfer pathways between the two enzymes. The sequence-structure-function correlations that differentiate hp53R2 and hRRM2 are revealed for the first time. Insight gained from this structural work will be used toward the identification of biological function, regulation mechanism and inhibitors selection in RNR small subunits.
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影响因子：
5.7
作者：
Zhou, BS;Shao, JM;Yen, Y
通讯作者：
Yen, Y
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
Cowtan, K
影响因子：
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作者：
Chabes, A;Thelander, L
通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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DOI：
10.1107/s0907444998012517
发表时间：
1999-02-01
影响因子：
2.2
作者：
Kissinger, CR;Gehlhaar, DK;Fogel, DB
通讯作者：
Fogel, DB