Batra Vinod K, Beard William A, Shock David D, Pedersen Lars C, Wilson Samuel H
Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Structure. 2005 Aug;13(8):1225-33. doi: 10.1016/j.str.2005.05.010.
DNA polymerases occasionally insert the wrong nucleotide. For this error to become a mutation, the mispair must be extended. We report a structure of DNA polymerase beta (pol beta) with a DNA mismatch at the boundary of the polymerase active site. The structure of this complex indicates that the templating adenine of the mispair stacks with the primer terminus adenine while the templating (coding) cytosine is flipped out of the DNA helix. Soaking the crystals of the binary complex with dGTP resulted in crystals of a ternary substrate complex. In this case, the templating cytosine is observed within the DNA helix and forms Watson-Crick hydrogen bonds with the incoming dGTP. The adenine at the primer terminus has rotated into a syn-conformation to interact with the opposite adenine in a planar configuration. Yet, the 3'-hydroxyl on the primer terminus is out of position for efficient nucleotide insertion.
DNA聚合酶偶尔会插入错误的核苷酸。要使这种错误成为一种突变，错配必须得以延伸。我们报道了一种在聚合酶活性位点边界处存在DNA错配的DNA聚合酶β（polβ）的结构。该复合物的结构表明，错配的模板腺嘌呤与引物末端腺嘌呤堆积在一起，而模板（编码）胞嘧啶则从DNA螺旋中翻转出来。用dGTP浸泡二元复合物晶体得到了三元底物复合物晶体。在这种情况下，观察到模板胞嘧啶位于DNA螺旋内，并与进入的dGTP形成沃森-克里克氢键。引物末端的腺嘌呤已旋转成顺式构象，以便以平面构型与相对的腺嘌呤相互作用。然而，引物末端的3'-羟基位置不当，不利于高效的核苷酸插入。
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