5ARJ

crystal structure of porcine RNase 4 D80A mutant

5ARJ の概要

• エントリーDOI: 10.2210/pdb5arj/pdb
• 関連するPDBエントリー: 5AR6 5ARK 5ARL
• 分子名称: RIBONUCLEASE 4 (1 entity in total)
• 機能のキーワード: hydrolase, rna degradation
• 由来する生物種: SUS SCROFA (PIG)
• 細胞内の位置: Secreted: P15468
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 62659.16

構造登録者

Liang, S.,Acharya, K.R. (登録日: 2015-09-25, 公開日: 2016-01-20, 最終更新日: 2024-10-23)

主引用文献

Liang, S.,Acharya, K.R.
Structural Basis of Substrate Specificity in Porcine Rnase 4.
FEBS J., 283:912-, 2016

PubMed Abstract: RNase 4, a member of the RNase A superfamily with substrate preference for uridine, has roles in host defence, angiogenesis and neurodegenerative diseases. It also exhibits the highest interspecies amino acid sequence similarity amongst RNase A family members. However, compared to other members of the RNase A family, including eosinophil-derived neurotoxin, eosinophil cationic protein and angiogenin, little is known about the molecular basis of substrate specificity in RNase 4. Here we report high to medium resolution structures of native porcine RNase 4 (PL3), a 'substrate-specificity' determining mutant D80A and their respective complexes with deoxyuridine 5'-monophosphate (dUMP) and deoxycytidine 5'-monophosphate (dCMP). These structures provide insight into the structural basis of the uridine versus cytosine substrate specificity in RNase 4: in the D80A mutant (D80A•dCMP), the side chain of Arg101 is positioned further away from the substrate-binding pocket due to the loss of the Asp80 side chain, reducing the repulsion force on the less favoured dCMP from Arg101 and allowing the ligand to occupy the binding pocket. This can also explain the observation that the ligand in the D80A•dCMP complex is stabilized only by a small number of hydrogen bonds. Compared to the previously reported structure of the human RNase 4•2'-deoxyuridine 3'-phosphate complex, the structure of PL3•dUMP complex shows additional hydrogen bonds between the ligand and the protein. In addition, the interaction between Arg101 and the dUMP ligand is absent. These observed differences are probably the result of the flexibility and different 'positioning' of the phosphate group among the mononucleotide ligands.

PubMed: 26748441
DOI: 10.1111/FEBS.13646

実験手法

X-RAY DIFFRACTION (2.9 Å)