Family I48
Summary for family I48
| Name | Inhibitor family I48 (clitocypin family) |
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| Family type peptidase | I48.001 - clitocypin (Lepista nebularis), MEROPS Accession MER0022482 (inhibitor unit: 1-150) |
| Content of family | Inhibitor family I48 contains inhibitors of cysteine endopeptidases. |
| History |
Identifier created: MEROPS 6.1 (10 January 2003)
Clitocypin was isolated from the fungus Lepista (formerly Clitocybe) nebularis by Brzin et al. (2000). |
| Peptidases inhibited | Peptidases inhibited are in family C1 ; they include papain (C01.001; Ki = 0.59 nM), cathepsin L (C01.032; Ki = 0.41 nM), cathepsin B (C01.060; Ki = 0.48 mu M), and stem bromelain (C01.005; Ki = 0.16 mu M) but not cathepsin H (C01.040). Trypsin (S01.151) and pepsin A (A01.001) are unaffected (Brzin et al., 2000). |
| Mechanism of inhibition | From the structure of the complex between clitocypin and cathepsin V (C01.009), the inhibitor forms a wedge that blocks the peptidase active site occluding the active site Cys. The narrow edge of the wedge is formed by two loops, the first stablized by a hydrogen bond (Arg12-Gly22) which interacts with nonprime substrate binding sites and the second containing a short helix which binds to the prime substrate binding sites. The mechanism of inhibitor is therefore similar to that of cystatins (I25). |
| Molecular structure | Clitocypin is a monomeric protein of 16.8 kDa. The sequence of about 150 residues does not include cysteine or methionine, so there are clearly no disulfide bonds, in contrast to many other families of inhibitors. The tertiary structure of clitocypin has been solved and shows a similar trefoil structure to macrocypin (I85.001), agglutinins and haemagglutins. Family I48 is the founder member of clan JI. Soybean Kunitz trypsin inhibitor (I03.001), a member of clan IC (Renko et al., 2010), has a similar beta-trefoil fold. |
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Distribution of family
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Viruses |
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