1M6J

CRYSTAL STRUCTURE OF TRIOSEPHOSPHATE ISOMERASE FROM ENTAMOEBA HISTOLYTICA

1M6J の概要

• エントリーDOI: 10.2210/pdb1m6j/pdb
• 分子名称: Triosephosphate Isomerase (2 entities in total)
• 機能のキーワード: asymmetry, entamoeba histolytica, monomer stability, triosephosphate isomerase, isomerase
• 由来する生物種: Entamoeba histolytica
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55929.84

構造登録者

Rodriguez-Romero, A.,Hernandez-Santoyo, A.,Fernandez-Velasco, D.A. (登録日: 2002-07-16, 公開日: 2002-10-12, 最終更新日: 2024-02-14)

主引用文献

Rodriguez-Romero, A.,Hernandez-Santoyo, A.,Del Pozo-Yauner, L.,Kornhauser, A.,Fernandez-Velasco, D.A.
Structure and Inactivation of Triosephosphate Isomerase from Entamoeba histolytica
J.Mol.Biol., 322:669-675, 2002

PubMed Abstract: Triosephosphate isomerase (TIM) has been proposed as a target for drug design. TIMs from several parasites have a cysteine residue at the dimer interface, whose derivatization with thiol-specific reagents induces enzyme inactivation and aggregation. TIMs lacking this residue, such as human TIM, are less affected. TIM from Entamoeba histolytica (EhTIM) has the interface cysteine residue and presents more than ten insertions when compared with the enzyme from other pathogens. To gain further insight into the role that interface residues play in the stability and reactivity of these enzymes, we determined the high-resolution structure and characterized the effect of methylmethane thiosulfonate (MMTS) on the activity and conformational properties of EhTIM. The structure of this enzyme was determined at 1.5A resolution using molecular replacement, observing that the dimer is not symmetric. EhTIM is completely inactivated by MMTS, and dissociated into stable monomers that possess considerable secondary structure. Structural and spectroscopic analysis of EhTIM and comparison with TIMs from other pathogens reveal that conformational rearrangements of the interface after dissociation, as well as intramonomeric contacts formed by the inserted residues, may contribute to the unusual stability of the derivatized EhTIM monomer.

PubMed: 12270704
DOI: 10.1016/S0022-2836(02)00809-4

実験手法

X-RAY DIFFRACTION (1.5 Å)