Table 3.

Summary of the predicted reactive Cys and Lys in the 15 kinases discussed in this work^a

Kinase	Family	Cys	Location	Reactivity	Major contributors	Lys	Location	Reactivity
FP Ncap Cys
BTK	Tec	C481	front pocket	reactive	N(+3), T(−71)	K430	roof	reactive
BMX	Tec	C479	β4 sheet	reactive		K445	roof	somewhat
		C496	front pocket	reactive	N(+3), R(+44)
		C549	β8 sheet	reactive
TEC	Tec	C406	αC helix	reactive
		C432	β4 sheet	reactive
		C449	front pocket	reactive	S(−71), N(+3), R(+44)
TXK	Tec	C333	β4 sheet	hyper
		C350	front pocket	somewhat	N(+3), R(+44)
		C402	β8 sheet	somewhat
ITK	Tec	C442	front pocket	reactive	S(+2), D(+3), R(+44)
JAK3	JakA	C909	front pocket	reactive	Y(−5), R(+2), R(+44)	K855	roof	hyper
		C1028	αG helix	reactive
MKK7	STE7	C147	P loop	hyper
		C218	front pocket	reactive	S(−74), K(+3)
		C276	DFG-1	reactive
		C341	loop (αF/αG)	hyper
EGFR	EGFR	C775	loop (αC/β4)	reactive
		C781	β4 sheet	reactive
ERBB2	EGFR	C789	β4 sheet	hyper		K860	DFG-3	reactive
ERBB4	EGFR	C891	A loop	reactive		K858	DFG-3	reactive
BLK	Src	C460	loop (αG/αH)	somewhat
FP Ncap+2 Cys
JNK1	MAPK	C116	front pocket	reactive	Q(+1), S(+39)
		C245		reactive	αH helix
JNK2	MAPK	C116	front pocket	reactive	Q(+1), S(+39)	K153	β7 sheet	somewhat
JNK3	MAPK	C154	front pocket	hyper	S(−82), Q(+1), S(+39)
		C283		reactive	loop (αG/αH)
CASK	CASK	C100	front pocket	somewhat

^aThe reactivity levels are defined in Table 2. Residues or locations that have been previously targeted by covalent inhibitors are labeled in bold font. Residues that make significant contributions to the pK_a shift of the Ncap Cys are listed with the sequence positions (relative to Ncap) given in the parenthesis. The calculated pK_a’s of all listed residues are given in Table S1.