Peptidase inhibitors in the MEROPS database

The Value of Fungal Protease Inhibitors in Affinity Chromatography

“…Commonly they are classified according to the class of protease they inhibit (for example: aspartic, cysteine or serine protease inhibitors) but a detailed classification of protein protease inhibitors based on their evolutionary relationship is available in the MEROPS database, together with a list of small molecule peptidase inhibitors (http://merops.sanger.ac.uk/inhibitors/). There are two general mechanisms by which protein inhibitors inhibit peptidases -irreversible "trapping" reaction, involving a conformational change of the inhibitor, and reversible tight-binding reactions, where the inhibitor forms a high-affinity interaction with the peptidase, most often at the active site (Christeller, 2005;Rawlings, 2010;Rawlings et al, 2004). The reversible protease inhibitors are used as ligands in affinity chromatography (Cuatrecasas et al, 1968).…”

“…Several other small molecule inhibitors with a broad inhibitory spectrum that are routinely used (e.g. pepstatin A, chymostatin, leupeptin, antipain, phosphoramidon, bestatin) were originally isolated from bacteria (Rawlings, 2010).…”

“…There are four families of serine protease inhibitors, namely the inhibitors of serine carboxypeptidase Y (family I51), Aspergillus elastase inhibitor family (I78), inhibitors of subtilisin-like proteases homologous to the subtilisin propeptide (family I9) and trypsin-specific protease inhibitors (family I66). Representatives of the latter two have been identified from higher fungi or mushrooms as well as from filamentous fungi (Rawlings, 2010). Furthermore, only three families of cysteine protease inhibitors have been described, namely mycocypins (families I48 and I85), that are unique to higher fungi, and a cysteine protease inhibitor family (I79) with only one representative found in one plant pathogenic fungal species (Rawlings, 2010).…”

β-Trefoil inhibitors – from the work of Kunitz onward

“…Correspondingly, the protein inhibitors may thus be deployed to regulate and prevent excessive proteolysis by endogenous proteases (reviewed by Turk et al , 2002 ;Turk , 2006 ;Lopez -Otin and Matrisian, 2007 ), defend against the attack of a pathogen or parasite (reviewed by Armstrong , 2001 ;Jongsma et al , 2008 ), or disable the proteolytic defense and repair mechanisms of the organism under attack (reviewed by . Because proteases have essential metabolic and regulatory functions in most biological processes, their protein inhibitors can be found in all forms of life (Rawlings , 2010 ).…”

“…The subsequent discoveries of protease inhibitors and the availability of the purifi ed and recombinant proteases led to the characterization of the inhibitors of proteases from various families and catalytic types, where some were also capable of inhibiting proteases from different families and clans. The latest review of inhibitors in the MEROPS database (Rawlings , 2010 ) indicates that of a total of 67 families that have been identifi ed, 24 inhibitor families are capable of inhibiting different protease families of one catalytic type and 11 families are capable of inhibiting proteases of different catalytic types.…”