کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10823949 | 1061955 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structural insight into the DNA polymerase β deoxyribose phosphate lyase mechanism
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
A large number of biochemical and genetic studies have demonstrated the involvement of DNA polymerase β (Pol β) in mammalian base excision repair (BER). Pol β participates in BER sub-pathways by contributing gap filling DNA synthesis and lyase removal of the 5â²-deoxyribose phosphate (dRP) group from the cleaved abasic site. To better understand the mechanism of the dRP lyase reaction at an atomic level, we determined a crystal structure of Pol β complexed with 5â²-phosphorylated abasic sugar analogs in nicked DNA. This DNA ligand represents a potential BER intermediate. The crystal structure reveals that the dRP group is bound in a non-catalytic binding site. The catalytic nucleophile in the dRP lyase reaction, Lys72, and all other potential secondary nucleophiles, are too far away to participate in nucleophilic attack on the C1â² of the sugar. An approximate model of the dRP group in the expected catalytic binding site suggests that a rotation of 120° about the dRP 3â²-phosphate is required to position the É-amino Lys72 close to the dRP C1â². This model also suggests that several other side chains are in position to facilitate the β-elimination reaction. From results of mutational analysis of key residues in the dRP lyase active site, it appears that the substrate dRP can be stabilized in the observed non-catalytic binding conformation, hindering dRP lyase activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 4, Issue 12, 8 December 2005, Pages 1347-1357
Journal: DNA Repair - Volume 4, Issue 12, 8 December 2005, Pages 1347-1357
نویسندگان
Rajendra Prasad, Vinod K. Batra, Xiao-Ping Yang, Joseph M. Krahn, Lars C. Pedersen, William A. Beard, Samuel H. Wilson,