Table 4 The selectivity of APPI-3M variants (normalized to the unmodified APPI-3M) toward KLK6 versus the three other proteases

From: Mapping protein selectivity landscapes using multi-target selective screening and next-generation sequencing of combinatorial libraries

Mutant

vs. mesotrypsin

vs. anionic trypsin

vs. cationic trypsin

Calculated KLK6 total selectivitya

Expected KLK6 total selectivityb

Unmodified APPI-3M

1

1

1

1

—

T11V/G17R

111.10

8.94

2.32

2304.13

242.45

T11S/G17R

31.62

3.87

0.94

115.53

32.33

T11S

2.14

0.30

0.12

0.08

—

T11V

0.64

1.58

0.60

0.60

—

G17R

32.26

7.42

1.69

404.09

—

  1. a \({{Calculated}}\,{{selectivity}} = \frac{{\frac{{Ki_{{{WT}}}\,{{for}}\,{{KLK}}6}}{{Ki_{{{mutant}}}\,{{for}}\,{{KLK}}6}}}}{{\frac{{Ki_{{{WT}}}\,{{for}}\,{{other}}\,{{protease}}\,{{in}}\,{{the}}\,{{pair}}}}{{Ki_{{{mutant}}}\,{{for}}\,{{other}}\,{{protease}}\,{{in}}\,{{the}}\,{{pair}}}}}}\)
  2. bExpected selectivity of double-mutant AB = calculated selectivity of A × calculated selectivity of B
Back to article page