The arginine finger of the Bloom syndrome protein: its structural organization and its role in energy coupling.
The arginine finger of the Bloom syndrome protein: its structural organization and its role in energy coupling.
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布卢姆综合征蛋白的精氨酸指：其结构组织及其在能量耦合中的作用
DOI：
10.1093/nar/gkm544
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发表时间：
2007
影响因子：
14.9
通讯作者：
Xi XG
中科院分区：
文献类型：
--
作者：
Ren H;Dou SX;Rigolet P;Yang Y;Wang PY;Amor-Gueret M;Xi XG
RecQ家族解旋酶在维持染色体DNA稳定性和完整性中是必不可少的。尽管进行了广泛的研究，这些酶的机制仍然知之甚少。许多解旋酶的晶体结构揭示了位于ATP的γ-磷酸附近的高度保守的精氨酸残基。该残基被广泛认为是精氨酸指，并且可以感知ATP结合和水解，并传递构象变化。我们研究了Bloom综合征蛋白（BLM），RecQ家族解旋酶，在ATP水解和能量耦合中精氨酸指的存在和作用。我们的研究结合结构建模，定点突变和生物化学和生物物理学的方法，证明与ATP的γ-磷酸或周围的ATP结合位点的相互作用的残基的突变导致在BLM的ATP酶活性的严重损害。这些突变也损害BLM的DNA解旋活动，但不影响其ATP和DNA结合能力。这些数据使我们能够确定R982作为BLM精氨酸指的残基。我们的研究结果进一步表明精氨酸指是如何精确定位的保守基序相对于γ-磷酸。
RecQ family helicases are essential in maintaining chromosomal DNA stability and integrity. Despite extensive studies, the mechanisms of these enzymes are still poorly understood. Crystal structures of many helicases reveal a highly conserved arginine residue located near the γ-phosphate of ATP. This residue is widely recognized as an arginine finger, and may sense ATP binding and hydrolysis, and transmit conformational changes. We investigated the existence and role of the arginine finger in the Bloom syndrome protein (BLM), a RecQ family helicase, in ATP hydrolysis and energy coupling. Our studies by combination of structural modelling, site-directed mutagenesis and biochemical and biophysical approaches, demonstrate that mutations of residues interacting with the γ-phosphate of ATP or surrounding the ATP-binding sites result in severe impairment in the ATPase activity of BLM. These mutations also impair BLM's DNA-unwinding activities, but do not affect its ATP and DNA-binding abilities. These data allow us to identify R982 as the residue that functions as a BLM arginine finger. Our findings further indicate how the arginine finger is precisely positioned by the conserved motifs with respect to the γ-phosphate.
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影响因子：
14.9
作者：
Killoran, Michael P.;Keck, James L.
通讯作者：
Keck, James L.
影响因子：
4.8
作者：
Dou, SX;Wang, PY;Xi, XG
通讯作者：
Xi, XG
DOI：
10.1016/0006-3002(60)91350-0
发表时间：
1960-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
AVRON, M
通讯作者：
AVRON, M
DOI：
10.1073/pnas.0400968101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Crampton, DJ;Guo, SY;Richardson, CC
通讯作者：
Richardson, CC
影响因子：
2.9
作者：
Nadanaciva, S;Weber, J;Senior, AE
通讯作者：
Senior, AE