<p>Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties. </p><p>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.</p><p>X-ray crystallography of a complex between the <taxon tax_id="615">Serratia marcescens</taxon> protease, SmaPI, and the inhibitor of <taxon tax_id="556">Erwinia chrysanthemi</taxon>, 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 [<cite idref="PUB00015040"/>, <cite idref="PUB00006323"/>].</p> <p> 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 [<cite idref="PUB00005013"/>]. 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 [<cite idref="PUB00000545"/>]. </p> Metalloprotease inhibitor I38