DNA apurinic-apyrimidinic site binding and excision by endonuclease IV

被引：88

作者：

Garcin, Elsa D.

Hosfield, David J.

Desai, Sunil A. ^{[2
]}

Haas, Brian J. ^{[2
]}

Bjoeras, Magnar

Cunningham, Richard P. ^{[2
]}

Tainer, John A. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[2] SUNY Albany, Dept Biol Sci, Albany, NY 12222 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2008年 / 15卷 / 05期

关键词：

D O I：

10.1038/nsmb.1414

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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-angstrom resolution DNA-free and the 2.45-angstrom 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-angstrom 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 alpha-beta triose phosphate isomerase (TIM) barrel and APE1 four-layer alpha-beta folds of the apurinic-apyrimidinic endonuclease families.

引用

页码：515 / 522

页数：8

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[1] Analysis of zinc binding sites in protein crystal structures [J].