2C34

Leishmania mexicana ICP

2C34 の概要

• エントリーDOI: 10.2210/pdb2c34/pdb
• NMR情報: BMRB: 6794
• 分子名称: INHIBITOR OF CYSTEINE PEPTIDASES (1 entity in total)
• 機能のキーワード: icp, chagasin, cysteine peptidase, inhibitor, immunoglobulin fold
• 由来する生物種: LEISHMANIA MEXICANA
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13035.05

構造登録者

Smith, B.O.,Picken, N.C.,Bromek, K.,Westrop, G.D.,Mottram, J.C.,Coombs, G.H. (登録日: 2005-10-04, 公開日: 2005-12-21, 最終更新日: 2024-05-15)

主引用文献

Smith, B.O.,Picken, N.C.,Westrop, G.D.,Bromek, K.,Mottram, J.C.,Coombs, G.H.
The Structure of Leishmania Mexicana Icp Provides Evidence for Convergent Evolution of Cysteine Peptidase Inhibitors.
J.Biol.Chem., 281:5821-, 2006

PubMed Abstract: Clan CA, family C1 cysteine peptidases (CPs) are important virulence factors and drug targets in parasites that cause neglected diseases. Natural CP inhibitors of the I42 family, known as ICP, occur in some protozoa and bacterial pathogens but are absent from metazoa. They are active against both parasite and mammalian CPs, despite having no sequence similarity with other classes of CP inhibitor. Recent data suggest that Leishmania mexicana ICP plays an important role in host-parasite interactions. We have now solved the structure of ICP from L. mexicana by NMR and shown that it adopts a type of immunoglobulin-like fold not previously reported in lower eukaryotes or bacteria. The structure places three loops containing highly conserved residues at one end of the molecule, one loop being highly mobile. Interaction studies with CPs confirm the importance of these loops for the interaction between ICP and CPs and suggest the mechanism of inhibition. Structure-guided mutagenesis of ICP has revealed that residues in the mobile loop are critical for CP inhibition. Data-driven docking models support the importance of the loops in the ICP-CP interaction. This study provides structural evidence for the convergent evolution from an immunoglobulin fold of CP inhibitors with a cystatin-like mechanism.

PubMed: 16407198
DOI: 10.1074/JBC.M510868200

実験手法

SOLUTION NMR