3IHZ

Crystal structure of the FK506 binding domain of Plasmodium vivax FKBP35 in complex with FK506

3IHZ の概要

• エントリーDOI: 10.2210/pdb3ihz/pdb
• 関連するPDBエントリー: 2VN1
• 分子名称: 70 kDa peptidylprolyl isomerase, putative, 8-DEETHYL-8-[BUT-3-ENYL]-ASCOMYCIN (3 entities in total)
• 機能のキーワード: plasmodium vivax, fkbp35, fk506, isomerase
• 由来する生物種: Plasmodium vivax
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28747.39

構造登録者

Qureshi, I.A.,Alag, R.,Yoon, H.S.,Lescar, J. (登録日: 2009-07-31, 公開日: 2010-06-16, 最終更新日: 2024-10-09)

主引用文献

Alag, R.,Qureshi, I.A.,Bharatham, N.,Shin, J.,Lescar, J.,Yoon, H.S.
NMR and crystallographic structures of the FK506 binding domain of human malarial parasite Plasmodium vivax FKBP35
Protein Sci., 19:1577-1586, 2010

PubMed Abstract: The emergence of drug-resistant malaria parasites is the major threat to effective malaria control, prompting a search for novel compounds with mechanisms of action that are different from the traditionally used drugs. The immunosuppressive drug FK506 shows an antimalarial activity. The mechanism of the drug action involves the molecular interaction with the parasite target proteins PfFKBP35 and PvFKBP35, which are novel FK506 binding protein family (FKBP) members from Plasmodium falciparum and Plasmodium vivax, respectively. Currently, molecular mechanisms of the FKBP family proteins in the parasites still remain elusive. To understand their functions, here we have determined the structures of the FK506 binding domain of Plasmodium vivax (PvFKBD) in unliganded form by NMR spectroscopy and in complex with FK506 by X-ray crystallography. We found out that PvFKBP35 exhibits a canonical FKBD fold and shares kinetic profiles similar to those of PfFKBP35, the homologous protein in P. falciparum, indicating that the parasite FKBP family members play similar biological roles in their life cycles. Despite the similarity, differences were observed in the ligand binding modes between PvFKBD and HsFKBP12, a human FKBP homolog, which could provide insightful information into designing selective antimalarial drug against the parasites.

PubMed: 20572013
DOI: 10.1002/pro.438

実験手法

X-RAY DIFFRACTION (1.67 Å)