4LYL

Crystal structure of uracil-DNA glycosylase from cod (Gadus morhua) in complex with the proteinaceous inhibitor UGI

4LYL の概要

• エントリーDOI: 10.2210/pdb4lyl/pdb
• 関連するPDBエントリー: 1OKB
• 分子名称: Uracil-DNA glycosylase, Uracil-DNA glycosylase inhibitor (3 entities in total)
• 機能のキーワード: alpha/beta fold, hydrolysis, intracellular, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Gadus morhua (Atlantic cod); 詳細
• 細胞内の位置: Mitochondrion: Q9I983
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 278164.67

構造登録者

Assefa, N.G.,Niiranen, L.M.K.,Johnson, K.A.,Leiros, H.-K.S.,Smalas, A.O.,Willassen, N.P.,Moe, E. (登録日: 2013-07-31, 公開日: 2014-08-13, 最終更新日: 2024-10-30)

主引用文献

Assefa, N.G.,Niiranen, L.,Johnson, K.A.,Leiros, H.K.,Smalas, A.O.,Willassen, N.P.,Moe, E.
Structural and biophysical analysis of interactions between cod and human uracil-DNA N-glycosylase (UNG) and UNG inhibitor (Ugi).
Acta Crystallogr.,Sect.D, 70:2093-2100, 2014

PubMed Abstract: Uracil-DNA N-glycosylase from Atlantic cod (cUNG) shows cold-adapted features such as high catalytic efficiency, a low temperature optimum for activity and reduced thermal stability compared with its mesophilic homologue human UNG (hUNG). In order to understand the role of the enzyme-substrate interaction related to the cold-adapted properties, the structure of cUNG in complex with a bacteriophage encoded natural UNG inhibitor (Ugi) has been determined. The interaction has also been analyzed by isothermal titration calorimetry (ITC). The crystal structure of cUNG-Ugi was determined to a resolution of 1.9 Å with eight complexes in the asymmetric unit related through noncrystallographic symmetry. A comparison of the cUNG-Ugi complex with previously determined structures of UNG-Ugi shows that they are very similar, and confirmed the nucleotide-mimicking properties of Ugi. Biophysically, the interaction between cUNG and Ugi is very strong and shows a binding constant (Kb) which is one order of magnitude larger than that for hUNG-Ugi. The binding of both cUNG and hUNG to Ugi was shown to be favoured by both enthalpic and entropic forces; however, the binding of cUNG to Ugi is mainly dominated by enthalpy, while the entropic term is dominant for hUNG. The observed differences in the binding properties may be explained by an overall greater positive electrostatic surface potential in the protein-Ugi interface of cUNG and the slightly more hydrophobic surface of hUNG.

PubMed: 25084329
DOI: 10.1107/S1399004714011699

実験手法

X-RAY DIFFRACTION (1.93 Å)