3SNF

Onconase, atomic resolution crystal structure

3SNF の概要

• エントリーDOI: 10.2210/pdb3snf/pdb
• 分子名称: Protein P-30, SULFATE ION, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: ribonuclease, alpha/beta, 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: 12385.01

構造登録者

Holloway, D.E.,Singh, U.P.,Shogen, K.,Acharya, K.R. (登録日: 2011-06-29, 公開日: 2011-10-05, 最終更新日: 2024-11-20)

主引用文献

Holloway, D.E.,Singh, U.P.,Shogen, K.,Acharya, K.R.
Crystal structure of Onconase at 1.1 angstrom resolution--insights into substrate binding and collective motion.
Febs J., 278:4136-4149, 2011

PubMed Abstract: Onconase(®) (ONC) is an amphibian member of the pancreatic ribonuclease superfamily that is selectively toxic to tumor cells. It is a much less efficient enzyme than the archetypal ribonuclease A and, in an attempt to gain further insight, we report the first atomic resolution crystal structure of ONC, determined in complex with sulfate ions at 100 K. The electron density map is of a quality sufficient to reveal significant nonplanarity in several peptide bonds. The majority of active site residues are very well defined, with the exceptions being Lys31 from the catalytic triad and Lys33 from the B(1) subsite, which are relatively mobile but rigidify upon nucleotide binding. Cryocooling causes a compaction of the unit cell and the protein contained within. This is principally the result of an inward movement of one of the lobes of the enzyme (lobe 2), which also narrows the active site cleft. Binding a nucleotide in place of sulfate is associated with an approximately perpendicular movement of lobe 2 and has little further effect on the cleft width. Aspects of this deformation are present in the principal axes of anisotropy extracted from C(α) atomic displacement parameters, indicating its intrinsic nature. The three lowest-frequency modes of ONC motion predicted by an anisotropic network model are compaction/expansion variations in which lobe 2 is the prime mover. Two of these have high similarity to the cryocooling response and imply that the essential 'breathing' motion of ribonuclease A is conserved in ONC. Instead, shifts in conformational equilibria may contribute to the reduced ribonucleolytic activity of ONC.

PubMed: 21895975
DOI: 10.1111/j.1742-4658.2011.08320.x

実験手法

X-RAY DIFFRACTION (1.1 Å)