3ITW

Crystal structure of TioX from Micromonospora sp. ML1

3ITW の概要

• エントリーDOI: 10.2210/pdb3itw/pdb
• 分子名称: Protein tioX (2 entities in total)
• 機能のキーワード: bleomycin resistance fold, bisintercalator, solvent-exposed trp residue, thiocoraline, protein binding, peptide binding protein
• 由来する生物種: Micromonospora sp. ML1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30941.36

構造登録者

Biswas, T.,Garneau-Tsodikova, S.,Tsodikov, O.V. (登録日: 2009-08-28, 公開日: 2010-02-16, 最終更新日: 2024-11-20)

主引用文献

Biswas, T.,Zolova, O.E.,Lombo, F.,de la Calle, F.,Salas, J.A.,Tsodikov, O.V.,Garneau-Tsodikova, S.
A New Scaffold of an Old Protein Fold Ensures Binding to the Bisintercalator Thiocoraline.
J.Mol.Biol., 397:495-507, 2010

PubMed Abstract: Thiocoraline is a thiodepsipeptide with potent antitumor activity. TioX, a protein with an unidentified function, is encoded by a gene of the thiocoraline biosynthetic gene cluster. The crystal structure of the full-length TioX protein at 2.15 A resolution reveals that TioX protomer shares an ancient betaalphabetabetabeta fold motif with glyoxalase I and bleomycin resistance protein families, despite a very low sequence homology. Intriguingly, four TioX monomers form a unique 2-fold symmetric tetrameric assembly that is stabilized by four intermolecular disulfide bonds formed cyclically between Cys60 and Cys66 of adjacent monomers. The arrangement of two of the four monomers in the TioX tetramer is analogous to that in dimeric bleomycin resistance proteins. This analogy indicates that this novel higher-order structural scaffold of TioX may have evolved to bind thiocoraline. Our equilibrium titration studies demonstrate the binding of a thiocoraline chromophore analog, quinaldic acid, to TioX, thereby substantiating this model. Furthermore, a strain of Streptomyces albus containing an exogenous thiocoraline gene cluster devoid of functional tioX maintains thiocoraline production, albeit with a lower yield. Taken together, these observations rule out a direct enzymatic function of TioX and suggest that TioX is involved in thiocoraline resistance or secretion.

PubMed: 20122935
DOI: 10.1016/j.jmb.2010.01.053

実験手法

X-RAY DIFFRACTION (2.15 Å)