A SINGLE 2'-HYDROXYL GROUP CONVERTS B-DNA TO A-DNA - CRYSTAL-STRUCTURE OF THE DNA-RNA CHIMERIC DECAMER DUPLEX D(CCGGC)R(G)D(CCGG) WITH A NOVEL INTERMOLECULAR G-CENTER-DOT-C BASE-PAIRED QUADRUPLET
A SINGLE 2'-HYDROXYL GROUP CONVERTS B-DNA TO A-DNA - CRYSTAL-STRUCTURE OF THE DNA-RNA CHIMERIC DECAMER DUPLEX D(CCGGC)R(G)D(CCGG) WITH A NOVEL INTERMOLECULAR G-CENTER-DOT-C BASE-PAIRED QUADRUPLET
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DOI：
10.1006/jmbi.1994.1134
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发表时间：
1994-02-11
影响因子：
5.6
通讯作者：
SUNDARALINGAM, M
中科院分区：
文献类型：
--
作者：
BAN, C;RAMAKRISHNAN, B;SUNDARALINGAM, M
我们发现，在B-DNA十聚体d（CCGGCGCCGG）的糖-磷酸骨架上引入一个2′-羟基可使其转变为A-DNA。因此，这是第一次在A和B-DNA构象中观察到相同序列的X射线结构，从而可以进行比较。DNA-RNA嵌合十聚体d（CCGGC）r（G）d（CCGG）的晶体属于正交晶系，空间群为P212121，晶胞尺寸a = 25·63 μ m，B= 45·24 μ m，c = 47·99 μ m，在不对称单元中有一个十聚体双链体。使用同晶结构d（CCCGGCCGGG）的坐标通过刚体搜索求解结构，并使用2753个独特的反射在1·9 μ m分辨率下将R值细化为0·136。最终的模型包含406个核苷酸原子和61个水分子。嵌合双链体具有典型的A-DNA几何构型，C（3′）端的所有糖都发生了内挤压，碱基对也发生了倾斜和移位。rG 6和rG 16上的2′-羟基突出到小沟表面并形成不同类型的氢键;链1上的2 ′-羟基与一个与糖基相关的C1残基的呋喃糖环O（4′）形成分子间氢键，而链2上的2 ′-羟基参与两个水桥。与下半部分相应的C7·G14碱基对相比，晶体堆积迫使双链体上半部分的G4·C17碱基对显着滑入小沟，导致这些碱基对表现出不同的碱基堆积和分子间相互作用。G4·C17碱基对的碱基G4形成一个非正统碱基“三联体”，G4*（G10·C11），通过其小沟位点N（2）和N（3）与一个糖基化相关分子的G10·C11碱基对的两个碱基的小沟原子N（2）和O（2）形成氢键。该三联体的碱基G10又与双链体的相邻碱基对G3·C18形成第二个类似的非正统碱基三联体，G10*（G3*C18），因此G10参与双重三联体。另一方面，在双链体的下半部分，C7·G14碱基对仅参与一个类似的非正统碱基三联体G20，（C7·G14）*G20，而相邻的碱基对rG 6·C15参与一个新的四联体C1·G20，（rG 6·C15）*（C1·G20），其中后者碱基对通过小沟位点G（N（2））... C（O（2））彼此氢键结合。双碱基三重和四重是首次观察到的特征。
We have found that the introduction of a single 2′-hydroxyl group on the sugar-phosphate backbone of theB-DNA decamer d(CCGGCGCCGG) transforms it toA-DNA. Thus, for the first time the X-ray structures of the same sequence have been observed in both theAandB-DNA conformations, permitting a comparison. Crystals of the DNA-RNA chimeric decamer d(CCGGC)r(G)d(CCGG) belong to the orthorhombic space groupP212121with unit cell dimensionsa= 25·63 Å,b= 45·24 Å andc= 47·99 Å, and one decamer duplex in the asymmetric unit. The structure was solved by a rigid body search using the coordinates of the isomorphous structure d(CCCGGCCGGG) and refined to anRvalue of 0·136 using 2753 unique reflections at 1·9 Å resolution. The final model contains 406 nucleotide atoms and 61 water molecules. The chimeric duplex exhibits typicalA-DNA geometry, with all the sugars in the C(3′)-endopuckering and the base-pairs inclined and displaced from the helix axis. The 2′-hydroxyl groups on rG6 and rG16 protrude into the minor groove surface and form different types of hydrogen bonds; that on strand 1 forms an intermolecular hydrogen bond with the furanose ring O(4′)of a symmetry-related C1 residue, while that on strand 2 is involved in two water bridges. Crystal packing forces the G4·C17 base-pair in the top half of the duplex to slide significantly into the minor groove compared to the corresponding C7·G14 base-pair in the bottom half, resulting in these base-pairs exhibiting different base stacking and intermolecular interactions. The base G4 of the G4·C17 base-pair forms an unorthodox base "triple", G4*(G10·C11), hydrogen-bonding through its minor groove sites N(2)and N(3)to the minor groove atoms N(2)and O(2)of both bases of the G10·C11 base-pair of a symmetry-related molecule. The base G10 of this triple in turn forms a second similar unorthodox base triple, G10*(G3*C18), with the adjacent base-pair G3·C18 of the duplex, thus G10 is involved in a double triple. On the other hand, in the bottom half of the duplex, the C7·G14 base pair is involved only in a single similar unorthodox base triple with G20, (C7·G14)*G20, while the adjacent base-pair rG6·C15 is involved in a novel quadruple with C1·G20, (rG6·C15)*(C1·G20), where the latter base-pairs are hydrogen-bonded to each otherviathe minor groove sites G(N(2))…C(O(2)). The double base triple and quadruple are features observed for the first time.