CRYSTAL-STRUCTURE OF DNA PHOTOLYASE FROM ESCHERICHIA-COLI

被引:476
作者
PARK, HW
KIM, ST
SANCAR, A
DEISENHOFER, J
机构
[1] UNIV TEXAS, SW MED CTR, HOWARD HUGHES MED INST, DALLAS, TX 75235 USA
[2] UNIV N CAROLINA, SCH MED, DEPT BIOCHEM & BIOPHYS, CHAPEL HILL, NC 27599 USA
关键词
D O I
10.1126/science.7604260
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Photolyase repairs ultraviolet (UV) damage to DNA by splitting the cyclobutane ring of the major UV photoproduct, the cis,syn-cyclobutane pyrimidine dimer (Pyr >$($) over bar Pyr). The reaction is initiated by blue light and proceeds through long-range energy transfer, single electron transfer, and enzyme catalysis by a radical mechanism. The three-dimensional crystallographic structure of DNA photolyase from Escherichia coli is presented and the atomic model was refined to an R value of 0.172 at 2.3 Angstrom resolution. The polypeptide chain of 471 amino acids is folded into an amino-terminal alpha/beta domain resembling dinucleotide binding domains and a carboxyl-terminal helical domain; a loop of 72 residues connects the domains. The light-harvesting cofactor 5,10-methenyltetrahydrofolylpolyglutamate (MTHF) binds in a cleft between the two domains. Energy transfer from MTHF to the catalytic cofactor flavin adenine dinucleotide (FAD) occurs over a distance of 16.8 Angstrom. The FAD adopts a U-shaped conformation between two helix clusters in the center of the helical domain and is accessible through a hole in the surface of this domain. Dimensions and polarity of the hole match those of a Pyr >$($) over bar Pyr dinucleotide, suggesting that the Pyr >$($) over bar Pyr ''flips out'' of the helix to fit into this hole, and that electron transfer between the flavin and the Pyr >$($) over bar Pyr occurs over van der Waals contact distance.
引用
收藏
页码:1866 / 1872
页数:7
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