4R1E

Crystal Structure of MTIP from Plasmodium falciparum in complex with a peptide-fragment chimera

4R1E の概要

• エントリーDOI: 10.2210/pdb4r1e/pdb
• 関連するPDBエントリー: 4AOM 4MZJ 4MZK 4MZL
• 分子名称: Myosin A tail domain interacting protein, Myosin-A, 5-{[(2-aminoethyl)sulfanyl]methyl}furan-2-carbaldehyde, ... (4 entities in total)
• 機能のキーワード: calmodulin-like, protein binding, myosin motor, fragment peptide, membrane, protein binding-inhibitor complex, protein binding/inhibitor
• 由来する生物種: Plasmodium falciparum; 詳細
• 細胞内の位置: Cell membrane ; Peripheral membrane protein ; Cytoplasmic side : Q8IDR3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18424.65

構造登録者

Douse, C.H.,Vrielink, N.,Cota, E.,Tate, E.W. (登録日: 2014-08-05, 公開日: 2014-11-12, 最終更新日: 2024-12-25)

主引用文献

Douse, C.H.,Vrielink, N.,Wenlin, Z.,Cota, E.,Tate, E.W.
Targeting a Dynamic Protein-Protein Interaction: Fragment Screening against the Malaria Myosin A Motor Complex.
Chemmedchem, 10:134-143, 2015

PubMed Abstract: Motility is a vital feature of the complex life cycle of Plasmodium falciparum, the apicomplexan parasite that causes human malaria. Processes such as host cell invasion are thought to be powered by a conserved actomyosin motor (containing myosin A or myoA), correct localization of which is dependent on a tight interaction with myosin A tail domain interacting protein (MTIP) at the inner membrane of the parasite. Although disruption of this protein-protein interaction represents an attractive means to investigate the putative roles of myoA-based motility and to inhibit the parasitic life cycle, no small molecules have been identified that bind to MTIP. Furthermore, it has not been possible to obtain a crystal structure of the free protein, which is highly dynamic and unstable in the absence of its natural myoA tail partner. Herein we report the de novo identification of the first molecules that bind to and stabilize MTIP via a fragment-based, integrated biophysical approach and structural investigations to examine the binding modes of hit compounds. The challenges of targeting such a dynamic system with traditional fragment screening workflows are addressed throughout.

PubMed: 25367834
DOI: 10.1002/cmdc.201402357

実験手法

X-RAY DIFFRACTION (1.98 Å)