02144nas a2200217   4500008004100000022001400041245014700055210006900202260007900271300001400350490000800364520126400372653002101636653002601657653002701683653003401710653002601744100001801770700001401788856012401802       2014                        eng d  a0273-228900aInteractions of a low molecular weight inhibitor from streptomyces sp. MBR04 with human cathepsin D: implications in mechanism of inactivation0 aInteractions of a low molecular weight inhibitor from streptomyc  a999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USAbHUMANA PRESS INCcNOV  a1705-17230 v1743 a<p>Cathepsin D, a lysosomal aspartic protease, is of potential interest as a target for drug design due to its implication in breast and ovarian cancer. The article reports a low molecular weight cathepsin D inhibitor from Streptomyces sp. MBR04. The M-r of the inhibitor was 1,078 Da as determined by MALDI-TOF, and the amino acid analysis showed the presence of Asp, Asp, Gly, Ala, Lys, Leu, Tyr, Trp residues. The steady-state kinetic interactions revealed reversible, competitive, slow-tight-binding nature of the inhibitor with an IC50 and K (i) values of 3.2 and 2.5 nM, respectively. The binding of the inhibitor with the enzyme and the subsequent conformational changes were monitored by exploiting the intrinsic fluorescence of the surface exposed Trp-54 residue. Based on the fluorescence and circular dichroism studies, we demonstrate that the inhibitor binds to the active site of cathepsin D and causes inactivation. All these kinetic, thermodynamic, and quenching studies suggest that the newly isolated peptidic inhibitor could be a potential scaffold to study and can be used to develop new potent therapeutic lead molecule for the development of drugs. The inhibitor will be significant as a potential lead molecule to target cathepsin D.</p>10aCancer treatment10aCathepsin D inhibitor10aInactivation mechanism10aSlow-tight-binding inhibition10aStreptomyces sp MBR041 aMenon, Vishnu1 aRao, Mala  uhttp://library.ncl.res.in/content/interactions-low-molecular-weight-inhibitor-streptomyces-sp-mbr04-human-cathepsin-d-0