2KAA

Solution Structure of Hirsutellin A from Hirsutella thompsonii

2KAA の概要

• エントリーDOI: 10.2210/pdb2kaa/pdb
• 分子名称: Hirsutellin A (1 entity in total)
• 機能のキーワード: ribotoxin, hirsutellin a, rip, alpha-sarcin, hirsutella thompsonii, toxin
• 由来する生物種: Hirsutella thompsonii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14509.43

構造登録者

Viegas, A.,Macedo, A.L.,Bruix, M. (登録日: 2008-11-04, 公開日: 2009-11-03, 最終更新日: 2024-10-16)

主引用文献

Viegas, A.,Herrero-Galan, E.,Onaderra, M.,Macedo, A.L.,Bruix, M.
Solution structure of hirsutellin A--new insights into the active site and interacting interfaces of ribotoxins.
Febs J., 276:2381-2390, 2009

PubMed Abstract: Hirsutellin (HtA) is intermediate in size between other ribotoxins and less specific microbial RNases, and thus offers a unique chance to determine the minimal structural requirements for activities unique to ribotoxins. Here, we have determined the structure of HtA by NMR methods. The structure consists of one alpha-helix, a helical turn and seven beta-strands that form an N-terminal hairpin and an anti-parallel beta-sheet, with a characteristic alpha + beta fold and a highly positive charged surface. Compared to its larger homolog alpha-sarcin, the N-terminal hairpin is shorter and less positively charged. The secondary structure elements are connected by large loops with root mean square deviation (rmsd) values > 1 A, suggesting some degree of intrinsically dynamic behavior. The active site architecture of HtA is unique among ribotoxins. Compared to alpha-sarcin, HtA has an aspartate group, D40, replacing a tyrosine, and the aromatic ring of F126, located in the leucine 'environment' close to the catalytic H113 in a similar arrangement to that found in RNase T1. This unique active site structure is discussed in terms of its novel electrostatic interactions to understand the efficient cytotoxic activity of HtA. The contributions of the N-terminal hairpin, loop 2 and loop 5 with regard to protein functionality, protein-protein and protein-ipid interactions, are also discussed. The truncation and reduced charge of the N-terminal hairpin in HtA may be compensated for by the extension and new orientation of its loop 5. This novel orientation of loop 5 re-establishes a positive charge on the side of the molecule that has been shown to be important for intermolecular interactions in ribotoxins.

PubMed: 19348010
DOI: 10.1111/j.1742-4658.2009.06970.x

実験手法

SOLUTION NMR