4IT7

Crystal structure of Al-CPI

Summary for 4IT7

• Entry DOI: 10.2210/pdb4it7/pdb
• Descriptor: CPI (2 entities in total)
• Functional Keywords: cpi, cystatin, hydrolase inhibitor
• Biological source: Ascaris lumbricoides (common roundworm)
• Total number of polymer chains: 4
• Total formula weight: 48182.71

Authors

Mei, G.Q.,Liu, S.L.,Sun, M.Z.,Liu, J. (deposition date: 2013-01-17, release date: 2014-01-29, Last modification date: 2014-06-11)

Primary citation

Mei, G.,Dong, J.,Li, Z.,Liu, S.,Liu, Y.,Sun, M.,Liu, G.,Su, Z.,Liu, J.
Structural Basis for the Immunomodulatory Function of Cysteine Protease Inhibitor from Human Roundworm Ascaris lumbricoides.
Plos One, 9:e96069-e96069, 2014

PubMed 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.

PubMed: 24781326
DOI: 10.1371/journal.pone.0096069

Experimental method

X-RAY DIFFRACTION (2.1 Å)