DNA apurinic-apyrimidinic site binding and excision by endonuclease IV

被引：0

作者：

Elsa D Garcin

David J Hosfield

Sunil A Desai

Brian J Haas

Magnar Björas

Richard P Cunningham

John A Tainer

机构：

[1] The Scripps Research Institute,Department of Molecular Biology and Skaggs Institute for Chemical Biology

[2] State University of New York at Albany,Department of Biological Sciences

[3] Present addresses: Takeda San Diego,undefined

[4] 10410 Science Center Drive,undefined

[5] San Diego,undefined

[6] California 92121,undefined

[7] USA (D.J.H.),undefined

[8] The Institute for Genomic Research,undefined

[9] 9712 Medical Center Drive,undefined

[10] Rockville,undefined

[11] Maryland 20850,undefined

[12] USA (B.J.H.) and Centre for Molecular Biology and Neuroscience,undefined

[13] Institute of Medical Microbiology,undefined

[14] Rikshospitalet University Hospital,undefined

[15] NO-0027 Oslo,undefined

[16] Norway (M.B.).,undefined

来源：

Nature Structural & Molecular Biology | 2008年 / 15卷

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摘要：

Escherichia coli endonuclease IV is an archetype for an abasic or apurinic-apyrimidinic endonuclease superfamily crucial for DNA base excision repair. Here biochemical, mutational and crystallographic characterizations reveal a three–metal ion mechanism for damage binding and incision. The 1.10-Å resolution DNA-free and the 2.45-Å resolution DNA-substrate complex structures capture substrate stabilization by Arg37 and reveal a distorted Zn3-ligand arrangement that reverts, after catalysis, to an ideal geometry suitable to hold rather than release cleaved DNA product. The 1.45-Å resolution DNA-product complex structure shows how Tyr72 caps the active site, tunes its dielectric environment and promotes catalysis by Glu261-activated hydroxide, bound to two Zn2+ ions throughout catalysis. These structural, mutagenesis and biochemical results suggest general requirements for abasic site removal in contrast to features specific to the distinct endonuclease IV α-β triose phosphate isomerase (TIM) barrel and APE1 four-layer α-β folds of the apurinic-apyrimidinic endonuclease families.

引用

页码：515 / 522

页数：7