Shen Betty W, Landthaler Markus, Shub David A, Stoddard Barry L
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N. A3-025, Seattle, WA 98109, USA.
J Mol Biol. 2004 Sep 3;342(1):43-56. doi: 10.1016/j.jmb.2004.07.032.
The structure of I-HmuI, which represents the last family of homing endonucleases without a defining crystallographic structure, has been determined in complex with its DNA target. A series of diverse protein structural domains and motifs, contacting sequential stretches of nucleotide bases, are distributed along the DNA target. I-HmuI contains an N-terminal domain with a DNA-binding surface found in the I-PpoI homing endonuclease and an associated HNH/N active site found in the bacterial colicins, and a C-terminal DNA-binding domain previously observed in the I-TevI homing endonuclease. The combination and exchange of these features between protein families indicates that the genetic mobility associated with homing endonucleases extends to the level of independent structural domains. I-HmuI provides an unambiguous structural connection between the His-Cys box endonucleases and the bacterial colicins, supporting the hypothesis that these enzymes diverged from a common ancestral nuclease.
I-HmuI是归巢内切酶家族中最后一个没有确定晶体结构的成员，其与DNA靶标的复合物结构已被确定。一系列不同的蛋白质结构域和基序沿着DNA靶标分布，与连续的核苷酸碱基片段相互作用。I-HmuI包含一个N端结构域，其具有在I-PpoI归巢内切酶中发现的DNA结合表面以及在细菌大肠菌素中发现的相关HNH/N活性位点，还有一个先前在I-TevI归巢内切酶中观察到的C端DNA结合结构域。这些特征在蛋白质家族之间的组合和交换表明，与归巢内切酶相关的遗传流动性延伸到了独立结构域的水平。I-HmuI在His-Cys框内切酶和细菌大肠菌素之间提供了明确的结构联系，支持了这些酶起源于共同祖先核酸酶的假说。
