Preferential Selectivity of Inhibitors with Human Tau Protein Kinase Gsk3𝜷 Elucidates Their Potential Roles for Off-Target Alzheimer’s Therapy

Table 5

Interaction of binding site residues amongst the 10 tau kinases with ATP.

GSK3β	CDK5	P38	ERK1/2	JNK	CK1d	DYRK1A	AKT	PKA	PKC	ATP binding site conservation across the 10 kinases
^#I 62 ^∗[4.4]	I10 [5.70]	V31 [4.24]	I 31 [5.59]	I 70 [4.23]	I 15-[2.36]	I 165-[3.09]	L156 [4.34]	L49 [4.10]	L345 [4.70]	I/V/L
^#G 63 ^∗[5.4]	G11 [4.7]	G32 [3.97]	G32 [>6]	G71 [4.31]	G16 [3.24]	G166 [5.12]	G157 [3.95]	G50 [4.88]	G346 [4.81]	G-well conserved
^#N 64 ^∗[5.24]	—	S33 [3.93]	E33 [>6]	—	—	K167 [4.60]	K158-[2.95]	T51 [2.76]	K347 [5.88]	Not conserved
^#G 65 ^∗[4.03]	—	G34 [3.36]	Y36 [2.79]	—	—	G168 [5.72]	G159 [5.08]	G52 [3.90]	G348 [>6]	Not conserved
^#S 66 ^∗[2.82]	—	A35 [3.64]	—	—	—	S169 [>6]	—	S53 [4.59]	S349 [5.81]	Not conserved
^#F 67 ^∗[3.21]	—	Y36 [3.17]	—	—	F20 [5.54]	F170 [>6]	F161 [5.54]	F54 [3.82]	—	Not conserved
^#V 70 ^∗[5.9]	V18-[2.72]	V39 [2.89]	V39 [2.79]	V78 [>6]	I 23 [5.07]	V173 [>6]	V164 [4.93]	V57 [2.88]	V353 [4.80]	V/I
^#A 83 ^∗[5.46]	A31 [4.61]	A52 [4.93]	A52 [4.64]	A91 [5.99]	A 36 [5.42]	A186 [5.00]	A177 [4.90]	A70 [4.49]	A366 [4.51]	A-well conserved
^#K 85 ^∗[2.64]	K33 [4.28]	K54-[2.67]	K54-[2.93]	K93 [5.18]	K38 [3.23]	K188 [3.19]	I179 [5.23]	K72-[3.72]	K368-[2.31]	K-well conserved
^#E 97 ^∗[4.59]	E51 [>6]	E72 [4.96]	E71 [3.71]	E111 [5.66]	E52 [3.78]	E203 [3.24]	E198 [4.93]	E91 [5.32]	E387 [3.45]	E-well conserved
^#V 110 ^∗[5.1]	V64 [>6]	I85 [>6]	I84 [>6]	I124 [>6]	P66 [>6]	V222 [5.80]	T211 [4.13]	V104 [5.40]	T401 [3.29]	V/I/P/T
^#L 132 ^∗[5.7]	F80 [4.31]	M107 [5.06]	Q105-[2.29]	M146-[2.18]	M82-[2.40]	F238 [4.71]	M227 [4.36]	M120 [4.50]	M417 [3.24]	F/Q/M
^#D 133 ^∗[2.58]	E81-[2.86]	P108-[2.49]	D106-[2.96]	E147 [5.39]	E-83-[2.83]	E239-[2.54]	E228-[2.88]	E121-[2.52]	E418-[3.05]	D/E-well conserved
^#Y 134 ^∗[3.9]	F82 [5.08]	F109 [4.65]	L107 [3.03]	L148 [3.63]	L84 [4.73]	M240 [3.57]	Y229 [3.81]	Y122 [5.50]	Y419 [3.44]	F/L/M/Y
^#V 135 ^∗[3.05]	C83-[3.19]	M110-[3.13]	M108-[3.03]	M149-[2.51]	L85-[2.97]	L241-[2.84]	A230-[3.20]	V123-[2.69]	V420-[2.64]	C/M/L/A/V
^#T 138 ^∗[5.6]	D86-[2.74]	D113-[2.89]	D111-[2.77]	N152-[2.45]	S88-[2.91]	N244 [4.37]	E 234-[2.63]	E127-[3.01]	D424-[2.99]	D/N/S/E
^#R 141 ^∗[3.10]	K89 [5.45]	K116 [5.32]	K 114 [3.92]	Q 155 [4.03]	D 91 [4.42]	D247 [5.51]	F237 [4.76]	S130 [5.50]	Y427 [>6]	R/K/Q/D/F/S/Y
^#Q 185 ^∗[2.98]	Q130-[2.66]	G 154 [4.71]	S153-[2.71]	S193 [4.42]	D132 [3.84]	E291 [4.66]	E278-[3.11]	E170 [2.30]	D467-[3.23]	Q/G/S/D/E
^#N 186 ^∗[3.45]	N131 [4.33]	N155 [>6]	N154 [3.98]	N194 [4.09]	N133 [2.88]	N292 [3.39]	N279 [5.38]	N171 [3.22]	N468 [4.22]	N-well conserved
^#L 188 ^∗[5.8]	L133 [5.76]	A157 [5.79]	L156 [>6]	V196 [>6]	L135 [5.29]	L294 [>6]	M281 [5.54]	L173 [5.88]	M470 [4.33]	L/A/V/M
^#C 199 ^∗[4.63]	A143 [5.93]	L167 [>6]	C166 [4.09]	L206 [5.20]	I148 [6.06]	V306 [2.70]	T291 [3.83]	T183 [3.62]	A480 [4.27]	C/A/L/I/V/T
^#D 200 ^∗[4.84]	N144 [3.72]	D168 [5.04]	D167 [3.79]	D207 [4.19]	D149 [2.97]	D307-[2.72]	D292 [3.11]	D184 [3.96]	D481-[2.59]	D-well conserved
22	16	19	16	15	18	18	21	22	18	Number of interacting residues with ATP within 6 Å

#Indicates residue type and number; *indicates distances in Angstroms.