9ICW

DNA POLYMERASE BETA (POL B) (E.C.2.7.7.7) COMPLEXED WITH SIX BASE PAIRS OF DNA; NATIVE STRUCTURE

9ICW の概要

• エントリーDOI: 10.2210/pdb9icw/pdb
• 関連するPDBエントリー: 1ZQA 1ZQB 1ZQC 1ZQD 1ZQE 1ZQF 1ZQG 1ZQH 1ZQI 1ZQJ 1ZQK 1ZQL 1ZQM 1ZQN 1ZQO 1ZQP 1ZQQ 1ZQR 1ZQS 1ZQT 7ICE 7ICF 7ICG 7ICH 7ICI 7ICJ 7ICK 7ICL 7ICM 7ICN 7ICO 7ICP 7ICQ 7ICR 7ICS 7ICT 7ICU 7ICV 8ICA 8ICB 8ICC 8ICE 8ICF 8ICG 8ICH 8ICI 8ICJ 8ICK 8ICL 8ICM 8ICN 8ICO 8ICP 8ICQ 8ICR 8ICS 8ICT 8ICU 8ICV 8ICW 8ICX 8ICY 8ICZ 9ICA 9ICB 9ICC 9ICE 9ICF 9ICG 9ICH 9ICI 9ICJ 9ICK 9ICL 9ICM 9ICN 9ICO 9ICP 9ICQ 9ICR 9ICS 9ICT 9ICU 9ICV 9ICX 9ICY
• 分子名称: DNA (5'-D(*CP*AP*TP*CP*TP*GP*T)-3'), DNA (5'-D(*CP*AP*GP*AP*TP*G)-3'), PROTEIN (DNA POLYMERASE BETA (E.C.2.7.7.7)), ... (6 entities in total)
• 機能のキーワード: dna-directed dna polymerase, dna replication, dna repair, nucleotidyltransferase, complex (nucleotidyltransferase-dna, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P06746
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 42305.35

構造登録者

Pelletier, H.,Sawaya, M.R. (登録日: 1995-12-16, 公開日: 1996-11-15, 最終更新日: 2023-08-02)

主引用文献

Pelletier, H.,Sawaya, M.R.,Wolfle, W.,Wilson, S.H.,Kraut, J.
Crystal structures of human DNA polymerase beta complexed with DNA: implications for catalytic mechanism, processivity, and fidelity
Biochemistry, 35:12742-12761, 1996

PubMed Abstract: Mammalian DNA polymerase beta (pol beta) is a small (39 kDa) DNA gap-filling enzyme that comprises an amino-terminal 8-kDa domain and a carboxy-terminal 31-kDa domain. In the work reported here, crystal structures of human pol beta complexed with blunt-ended segments of DNA show that, although the crystals belong to a different space group, the DNA is nevertheless bound in the pol beta binding channel in the same way as the DNA in previously reported structures of rat pol beta complexed with a template-primer and ddCTP [Pelletier, H., Sawaya, M. R., Kumar, A., Wilson, S. H., & Kraut, J. (1994) Science 264, 1891-1903]. The 8-kDa domain is in one of three previously observed positions relative to the 31-kDa domain, suggesting that the 8-kDa domain may assume only a small number of stable conformations. The thumb subdomain is in a more open position in the human pol beta-DNA binary complex than it is in the rat pol beta-DNA-ddCTP ternary complex, and a closing thumb upon nucleotide binding could represent the rate-limiting conformational change that has been observed in pre-steady-state kinetic studies. Intermolecular contacts between the DNA and the 8-kDa domain of a symmetry-related pol beta molecule reveal a plausible binding site on the 8-kDa domain for the downstream oligonucleotide of a gapped-DNA substrate; in addition to a lysine-rich binding pocket that accommodates a 5'-PO4 end group, the 8-kDa domain also contains a newly discovered helix-hairpin-helix (HhH) motif that binds to DNA in the same way as does a structurally and sequentially homologous HhH motif in the 31-kDa domain. DNA binding by both HhH motifs is facilitated by a metal ion. In that HhH motifs have been identified in other DNA repair enzymes and DNA polymerases, the HhH-DNA interactions observed in pol beta may be applicable to a broad range of DNA binding proteins. The sequence similarity between the HhH motif of endonuclease III from Escherichia coli and the HhH motif of the 8-kDa domain of pol beta is particularly striking in that all of the conserved residues are clustered in one short sequence segment, LPGVGXK, where LPGV corresponds to a type II beta-turn (the hairpin turn), and GXK corresponds to a part of the HhH motif that is proposed to be critical for DNA binding and catalysis for both enzymes. These results suggest that endonuclease III and the 8-kDa domain of pol beta may employ a similar mode of DNA binding and may have similar catalytic mechanisms for their respective DNA lyase activities. A model for productive binding of pol beta to a gapped-DNA substrate requires a 90 degrees bend in the single-stranded template, which could enhance nucleotide selectivity during DNA repair or replication.

PubMed: 8841118
DOI: 10.1021/bi952955d

実験手法

X-RAY DIFFRACTION (2.6 Å)