Mastering the canonical loop of serine protease inhibitors: enhancing potency by optimising the internal hydrogen bond network.

ABSTRACT:

Background

Canonical serine protease inhibitors commonly bind to their targets through a rigid loop stabilised by an internal hydrogen bond network and disulfide bond(s). The smallest of these is sunflower trypsin inhibitor (SFTI-1), a potent and broad-range protease inhibitor. Recently, we re-engineered the contact β-sheet of SFTI-1 to produce a selective inhibitor of kallikrein-related peptidase 4 (KLK4), a protease associated with prostate cancer progression. However, modifications in the binding loop to achieve specificity may compromise structural rigidity and prevent re-engineered inhibitors from reaching optimal binding affinity.

Methodology/principal findings

In this study, the effect of amino acid substitutions on the internal hydrogen bonding network of SFTI were i

SUBMITTER: Swedberg JE 

PROVIDER: S-EPMC3083445 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature