Metalloprotease inhibitor I38 (IPR003086)

Short name: MPTase_inhib_I38

Overlapping homologous superfamilies

Domain relationships


This family of proteins represent monomeric serralysin inhibitors of about 125 residues, which interact with specific metalloprotease which are synthesised by serralysin secretors and characterised by being plant, insect and animal pathogens. It is probable that the serralysin inhibitors protect the host from proteolysis during export of the protease. The members of this family belong to MEROPS proteinase inhibitor family I38, clan IK.

X-ray crystallography of a complex between the Serratia marcescens protease, SmaPI, and the inhibitor of Erwinia chrysanthemi, Inh, reveals that Inh is folded into an eight-stranded b-barrel with an N-terminal trunk of 10 residues. Residues 1-5 occupy part of the extended active site of the proteinase, thereby preventing access of the substrate. Residues 6-10 form a linker that connects the N-terminal proteinase-binding peptide to the body of the b-barrel. The backbone carbonyl of Ser-1 interacts with the catalytic zinc; the Ser-2 side chain occupies the S1'-binding site and also forms a hydrogen bond to the carboxyl end of the catalytic Glu, whereas Leu-3 occupies the S2' recognition site. Penetration of the trunk region further than 5 residues into the substrate binding cleft appears to be prevented by the b-barrel, which itself interacts with the proteinase near its Met turn (19). Peptide mimetics of the trunk at concentrations up to about 100 mM do not inhibit the protease, demonstrating that the barrel is essential for inhibitory activity [PMID: 10770939, PMID: 7752231].

Structurally and functionally these inhibitors are closely related to the lipocalins, fatty acid-binding proteins, avidins and the enigmatic triabin. Together these five protein families constitute the calycin superfamily [PMID: 7684291]. The proteins are characterised by their high specificity for small hydrophobic molecules and by their ability to form complexes with soluble macromolecules either through intramolecular disulphides or protein-protein interactions [PMID: 8761444].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0004866 endopeptidase inhibitor activity

Cellular Component

GO:0030288 outer membrane-bounded periplasmic space

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.