PDBsum entry 4it7

Hydrolase inhibitor

PDB id: 4it7

Contents

Protein chains

107 a.a.

Waters ×126

PDB id:

4it7

Name:

Hydrolase inhibitor

Title:

Crystal structure of al-cpi

Structure:

Cpi. Chain: a, b, c, d. Synonym: cysteine protease inhibitor. Engineered: yes

Source:

Ascaris lumbricoides. Common roundworm. Organism_taxid: 6252. Gene: cpi. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.10Å R-factor: 0.204 R-free: 0.257

Authors:

G.Q.Mei,S.L.Liu,M.Z.Sun,J.Liu

Key ref:

G.Mei et al. (2014). Structural basis for the immunomodulatory function of cysteine protease inhibitor from human roundworm Ascaris lumbricoides. Plos One, 9, e96069. PubMed id: 24781326 DOI: 10.1371/journal.pone.0096069

Date:

17-Jan-13 Release date: 29-Jan-14

Protein chains

E9N3T6  (E9N3T6_ASCLU) -  CPI from Ascaris lumbricoides

Seq: 132 a.a.

Struc: 107 a.a.

DOI no: 10.1371/journal.pone.0096069

Plos One 9:e96069 (2014)

PubMed id: 24781326

Structural basis for the immunomodulatory function of cysteine protease inhibitor from human roundworm Ascaris lumbricoides.

G.Mei, J.Dong, Z.Li, S.Liu, Y.Liu, M.Sun, G.Liu, Z.Su, J.Liu.

ABSTRACT

Immunosuppression associated with infections of nematode parasites has been documented. Cysteine protease inhibitor (CPI) released by the nematode parasites is identified as one of the major modulators of host immune response. In this report, we demonstrated that the recombinant CPI protein of Ascaris lumbricoides (Al-CPI) strongly inhibited the activities of cathepsin L, C, S, and showed weaker effect to cathepsin B. Crystal structure of Al-CPI was determined to 2.1 Å resolution. Two segments of Al-CPI, loop 1 and loop 2, were proposed as the key structure motifs responsible for Al-CPI binding with proteases and its inhibitory activity. Mutations at loop 1 and loop 2 abrogated the protease inhibition activity to various extents. These results provide the molecular insight into the interaction between the nematode parasite and its host and will facilitate the development of anthelmintic agents or design of anti-autoimmune disease drugs.