2R9B

Structural Analysis of Plasmepsin 2 from Plasmodium falciparum complexed with a peptide-based inhibitor

2R9B の概要

• エントリーDOI: 10.2210/pdb2r9b/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000306
• 分子名称: Plasmepsin-2, peptide-based inhibitor (3 entities in total)
• 機能のキーワード: beta fold aspartyl protease, glycoprotein, vacuole, zymogen, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Plasmodium falciparum; 詳細
• 細胞内の位置: Vacuole: P46925
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75839.86

構造登録者

Liu, P.,Marzahn, M.R.,Robbins, A.H.,McKenna, R.,Dunn, B.M. (登録日: 2007-09-12, 公開日: 2007-11-27, 最終更新日: 2023-11-15)

主引用文献

Liu, P.,Marzahn, M.R.,Robbins, A.H.,Gutierrez-de-Teran, H.,Rodriguez, D.,McClung, S.H.,Stevens, S.M.,Yowell, C.A.,Dame, J.B.,McKenna, R.,Dunn, B.M.
Recombinant plasmepsin 1 from the human malaria parasite plasmodium falciparum: enzymatic characterization, active site inhibitor design, and structural analysis.
Biochemistry, 48:4086-4099, 2009

PubMed Abstract: A mutated form of truncated proplasmepsin 1 (proPfPM1) from the human malaria parasite Plasmodium falciparum, proPfPM1 K110pN, was generated and overexpressed in Escherichia coli. The automaturation process was carried out at pH 4.0 and 4.5, and the optimal catalytic pH of the resulting mature PfPM1 was determined to be pH 5.5. This mature PfPM1 showed comparable binding affinity to peptide substrates and inhibitors with the naturally occurring form isolated from parasites. The S3-S3' subsite preferences of the recombinant mature PfPM1 were explored using combinatorial chemistry based peptide libraries. On the basis of the results, a peptidomimetic inhibitor (compound 1) was designed and yielded 5-fold selectivity for binding to PfPM1 versus the homologous human cathepsin D (hcatD). The 2.8 A structure of the PfPM2-compound 1 complex is reported. Modeling studies were conducted using a series of peptidomimetic inhibitors (compounds 1-6, Table 3) and three plasmepsins: the crystal structure of PfPM2, and homology derived models of PfPM1 and PfPM4.

PubMed: 19271776
DOI: 10.1021/bi802059r

実験手法

X-RAY DIFFRACTION (2.8 Å)