1YV7

X-ray structure of (C87S,des103-104) onconase

1YV7 の概要

• エントリーDOI: 10.2210/pdb1yv7/pdb
• 関連するPDBエントリー: 1YV4 1YV6
• 分子名称: P-30 protein, SULFATE ION (3 entities in total)
• 機能のキーワード: small conformational changes, onconase thermal stability, ribonucleases, antitumor action, dynamics, hydrolase
• 由来する生物種: Rana pipiens (northern leopard frog)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11735.42

構造登録者

Merlino, A.,Mazzarella, L.,Carannante, A.,Di Fiore, A.,Di Donato, A.,Notomista, E.,Sica, F. (登録日: 2005-02-15, 公開日: 2005-03-01, 最終更新日: 2024-10-09)

主引用文献

Merlino, A.,Mazzarella, L.,Carannante, A.,Di Fiore, A.,Di Donato, A.,Notomista, E.,Sica, F.
The Importance of Dynamic Effects on the Enzyme Activity: X-RAY STRUCTURE AND MOLECULAR DYNAMICS OF ONCONASE MUTANTS
J.Biol.Chem., 280:17953-17960, 2005

PubMed Abstract: Onconase (ONC), a member of the RNase A superfamily extracted from oocytes of Rana pipiens, is an effective cancer killer. It is currently used in treatment of various forms of cancer. ONC antitumor properties depend on its ribonucleolytic activity that is low in comparison with other members of the superfamily. The most damaging side effect from Onconase treatment is renal toxicity, which seems to be caused by the unusual stability of the enzyme. Therefore, mutants with reduced thermal stability and/or increased catalytic activity may have significant implications for human cancer chemotherapy. In this context, we have determined the crystal structures of two Onconase mutants (M23L-ONC and C87S,des103-104-ONC) and performed molecular dynamic simulations of ONC and C87S,des103-104-ONC with the aim of explaining on structural grounds the modifications of the activity and thermal stability of the mutants. The results also provide the molecular bases to explain the lower catalytic activity of Onconase compared with RNase A and the unusually high thermal stability of the amphibian enzyme.

PubMed: 15728177
DOI: 10.1074/jbc.M501339200

実験手法

X-RAY DIFFRACTION (1.9 Å)