4X2T

X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M17 Leucyl Aminopeptidase from P. falciparum

4X2T の概要

• エントリーDOI: 10.2210/pdb4x2t/pdb
• 関連するPDBエントリー: 3KQX 3KQZ 3KR4 4X2U
• 分子名称: M17 leucyl aminopeptidase, ZINC ION, (2S)-({(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}amino)(phenyl)ethanoic acid, ... (7 entities in total)
• 機能のキーワード: m17 leucyl-aminopeptidase, protease, inhibitor, tosedostat, antimalarial, plasmodium falciparum, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 700419.22

構造登録者

Drinkwater, N.,McGowan, S. (登録日: 2014-11-27, 公開日: 2015-02-18, 最終更新日: 2024-10-30)

主引用文献

Drinkwater, N.,Bamert, R.S.,Sivaraman, K.K.,Paiardini, A.,McGowan, S.
X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17.
Proteins, 83:789-795, 2015

PubMed Abstract: New anti-malarial treatments are desperately required to face the spread of drug resistant parasites. Inhibition of metalloaminopeptidases, PfA-M1 and PfA-M17, is a validated therapeutic strategy for treatment of Plasmodium falciparum malaria. Here, we describe the crystal structures of PfA-M1 and PfA-M17 bound to chemotherapeutic agent Tosedostat. The inhibitor occupies the enzymes' putative product egress channels in addition to the substrate binding pockets; however, adopts different binding poses when bound to PfA-M1 and PfA-M17. These findings will be valuable for the continued development of selective inhibitors of PfA-M1 and PfA-M17.

PubMed: 25645579
DOI: 10.1002/prot.24771

実験手法

X-RAY DIFFRACTION (2.729 Å)