Dalhus Bjørn, Arvai Andrew S, Rosnes Ida, Olsen Øyvind E, Backe Paul H, Alseth Ingrun, Gao Honghai, Cao Weiguo, Tainer John A, Bjørås Magnar
Centre for Molecular Biology and Neuroscience, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo, Norway.
Nat Struct Mol Biol. 2009 Feb;16(2):138-43. doi: 10.1038/nsmb.1538. Epub 2009 Jan 11.
Endonuclease V (EndoV) initiates a major base-repair pathway for nitrosative deamination resulting from endogenous processes and increased by oxidative stress from mitochondrial dysfunction or inflammatory responses. We solved the crystal structures of Thermotoga maritima EndoV in complex with a hypoxanthine lesion substrate and with product DNA. The PYIP wedge motif acts as a minor groove-damage sensor for helical distortions and base mismatches and separates DNA strands at the lesion. EndoV incises DNA with an unusual offset nick 1 nucleotide 3' of the lesion, as the deaminated adenine is rotated approximately 90 degrees into a recognition pocket approximately 8 A from the catalytic site. Tight binding by the lesion-recognition pocket in addition to Mg(2+) and hydrogen-bonding interactions to the DNA ends stabilize the product complex, suggesting an orderly recruitment of downstream proteins in this base-repair pathway.
核酸内切酶V（EndoV）启动了一条主要的碱基修复途径，用于修复内源性过程导致的亚硝化脱氨作用，并且线粒体功能障碍或炎症反应产生的氧化应激会增强这种作用。我们解析了嗜热栖热菌EndoV与次黄嘌呤损伤底物及产物DNA形成复合物的晶体结构。PYIP楔形基序作为小沟损伤传感器，用于检测螺旋扭曲和碱基错配，并在损伤处分离DNA链。EndoV在损伤位点3'端1个核苷酸处产生一个不寻常的错位切口来切割DNA，因为脱氨基的腺嘌呤会旋转约90度进入距催化位点约8埃的识别口袋。损伤识别口袋的紧密结合以及与DNA末端的镁离子（Mg²⁺）和氢键相互作用稳定了产物复合物，这表明在这条碱基修复途径中，下游蛋白会有序募集。
