Publication Date:
1995-06-30
Description:
Photolyase repairs ultraviolet (UV) damage to DNA by splitting the cyclobutane ring of the major UV photoproduct, the cis, syn-cyclobutane pyrimidine dimer (Pyr 〈〉 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 A 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 A. 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 〈〉 Pyr dinucleotide, suggesting that the Pyr 〈〉 Pyr "flips out" of the helix to fit into this hole, and that electron transfer between the flavin and the Pyr 〈〉 Pyr occurs over van der Waals contact distance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, H W -- Kim, S T -- Sancar, A -- Deisenhofer, J -- GM31082/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Jun 30;268(5219):1866-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7604260" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Computer Graphics
;
Crystallography, X-Ray
;
DNA Damage
;
DNA Repair
;
DNA, Bacterial/metabolism
;
Deoxyribodipyrimidine Photo-Lyase/*chemistry/metabolism
;
Electron Transport
;
Escherichia coli/*enzymology
;
Flavin-Adenine Dinucleotide/metabolism
;
Folic Acid/analogs & derivatives/metabolism
;
Hydrogen Bonding
;
Models, Molecular
;
Molecular Sequence Data
;
Protein Conformation
;
Protein Folding
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Pyrimidine Dimers/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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