Table 1. Design of I10H Analogues.

KLK5 Motifs a	I10H Analogues b	Modification	Potential Interactions
HPGHS (green region Fig 2)	GRCTKSIPPHCYPD	F→Y (F12Y)	hydrogen bond between hydroxyl of tyrosine and nitrogen of histidine
HPGHS (green region Fig 2)	GRCTKSIPPHCWPD	F→W (F12W)	π-π stacking between tryptophan and histidine or hydrogen-π interaction
PNQLY (blue region Fig 2)	GRCTKSKPPHCFPD	I→K (I7K)	hydrogen bond between NH of lysine and C = O of asparagine side chain
SWGDYP (red region Fig 2)	NRCTKSIPPHCFPD	G→N (G1N)	hydrogen bond between C = O of aspartate and NH of asparagine side chain
The Substrate Pocket (magenta region Fig 2)	GRCTRSIPPHCFPD	K→R (K5R)	Substrate binding pocket of KLK5 is predicted to have preference for arginine [33]

^a Letters in bold are the amino acid residues that were expected to form the interactions.

^b Letters in bold are the additional substitutions on the I10H sequence.