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Sequence conservation in the chagasin family suggests a common trend in cysteine proteinase binding by unrelated protein inhibitors
Author(s) -
Rigden Daniel J.,
Mosolov Vladimir V.,
Galperin Michael Y.
Publication year - 2002
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0207202
Subject(s) - cysteine , proteases , biochemistry , papain , conserved sequence , biology , peptide sequence , cysteine proteinase inhibitors , cysteine protease , structural motif , cystatin , enzyme , cystatin c , gene , apoptosis , programmed cell death , caspase , renal function
The recently described inhibitor of cysteine proteinases from Trypanosoma cruzi , chagasin, was found to have close homologs in several eukaryotes, bacteria and archaea, the first protein inhibitors of cysteine proteases in prokaryotes. These previously uncharacterized 110–130 residue‐long proteins share a well‐conserved sequence motif that corresponds to two adjacent β‐strands and the short loop connecting them. Chagasin‐like proteins also have other conserved, mostly aromatic, residues, and share the same predicted secondary structure. These proteins adopt an all‐β fold with eight predicted β‐strands of the immunoglobulin type. The phylogenetic distribution of the chagasins generally correlates with the presence of papain‐like cysteine proteases. Previous studies have uncovered similar trends in cysteine proteinase binding by two unrelated inhibitors, stefin and p41, that belong to the cystatin and thyroglobulin families, respectively. A hypothetical model of chagasin–cruzipain interaction suggests that chagasin may dock to the cruzipain active site in a similar manner with the conserved NPTTG motif of chagasin forming a loop that is similar to the wedge structures formed at the active sites of papain and cathepsin L by stefin and p41.