title: Slow-tight binding inhibition of pepsin by an aspartic protease inhibitor from Streptomyces sp. MBR04.
abstract: The present article reports a low molecular weight aspartic protease inhibitor from a Streptomyces sp. MBR04 exhibiting a two-step inhibition mechanism against pepsin. The kinetic interactions revealed a reversible, competitive, slow-tight binding inhibition with an IC(50) and K(i) values of 4.5 nM and 4 nM respectively. The conformational changes induced upon inhibitor binding to pepsin was monitored by far and near UV analysis, demonstrated that the inhibitor binds to the active site and causes inactivation. Chemical modification of the inhibitor with WRK and TNBS abolished the antiproteolytic activity of the inhibitor.
authors.affiliation: Division of Biochemical Sciences, National Chemical Laboratory, Pune 411008, India.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Menon
authors.forename: Mala
authors.initials: M
authors.lastname: Rao
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D057055:Aspartic Acid Proteases / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D010434:Pepsin A / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D059748:Proteolysis / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011480:Protease Inhibitors; D000244:Adenosine Diphosphate; D057055:Aspartic Acid Proteases; D010434:Pepsin A