Checking the Ki values of the used X-ray structures for the urokinase COMBINE model

For some of the Ki values (given in M) a inconsistents could be found. After checking the corresponding articles the old Ki values (bold numbers of column 'alt Ki exp' in table) were changed (see column neu Ki). The ligands were grouped into three parts based on the different research groups (yellow: Katz et al., blue: Strzebecher et al., grey: Wendt et al.). The values for A25 and A28 were identified as outliers.

The ligands can split into the following groups (ligands in brackets should not used because of potential inconsistancy of the Ki values):
Katz Strzebecher Wendt
# 12 (13) # 6 (7) # 9 (10)
A04 (A20) (A29)
A12 A25 A30
A13 A26 A31
A14 A28 A32
A15 A39 A33
A16 A40 A34
A17 A41 A35
A18
A36
A19
A37
(A20)
A38
A21

A23

A24




ID residue PDB PDB Ref #
dGexp alt Kiexp neu Ki MOAD Ki conditions KiRef Ki conditions KiRef Ki conditions KiRef



14 A04 1o5a JMB2004,344 8696 Ala190 -9.739 0.072 0.072 0.072 pH 7,4 JMB2003,93




8 A12 1gi8


-6.886 8.9 7.2 8.9 pH 7,4 JMB2003,93 5.5 pH 7,4, -Zn JMC2001,44 2.65 pH 7,4, +Zn JMC2001,44

12 A13 1gi9
6669
-7.12 6 4.95 1.1 6 pH 7,4 JMB2003,93 3.9 pH 7,4, -Zn JMC2001,44 1.1 Ki min,pH 8 JMB2001,307

13 A14 1gjb
7806
-8.654 0.45 0.425 0.45 0.45 pH 7,4, EDTA JMB2003,93 0.4 pH 7.4, -Zn JMC2001,44 0.54 pH 7,4, +Zn JMC2001,44


1gjc
8696
-8.654
0.425 0.008 0.45 pH 7,4, EDTA JMB2003,93 0.4 pH 7.4, -Zn JMC2001,44 0.54 pH 7,4, +Zn JMC2001,44

2 A15 1o3p
10655
-9.077 0.22 0.22 0.22 0.22 pH 7.4 JMB2003,93




4 A16 1gj8
10950
-9.488 0.11 0.11 0.11 0.11 pH 7.4 JMB2003,93 0.11 pH 7.4 ChemBio2001,8 2 pH 8.2, +Zn ChemBio2001,8 0.16 pH 8.2, EDTA ChemBio2001,8
7 A17 1o5c
11092
-10.2 0.033 0.033 0.033 pH 7.4 JMB2003,93




1 A18 1gj7
10302
-10.75 0.013 0.011 0.009 0.013 pH 7.4 JMB2003,93 0.009 pH 7.4, EDTA ChemBio2001,8 0.008 -Zn JMC2001,44 0.01 +Zn JMC2001,44
159 A19 1c5x
6860
-9.105 0.21 0.21 0.21
BioorgMedChem2002,12 0.21 ChemBio2000,7



1c5w
6860
-9.105
0.21
BioorgMedChem2002,12 0.21 ChemBio2000,7



105b
6860
-9.105
0.21
BioorgMedChem2002,12 0.21 ChemBio2000,7


160 A20 1c5z
benzamidine
-7.228 5 97 180 5 pH 7.8 min JMB2001,307 180
JMB2000,301 97
ChemBio2000,7


1f5k
benzamidine
-7.228
180 180 5 pH 7.8 min JMB2001,307 180
JMB2000,301 97
ChemBio2000,7

161 A21 1c5y
7538
-5.727 63 63 63
ChemBio2000,7




162 A22 1gi7
10273
-6.147 31 31 31 31 pH 5.7 min JMB2001,307




163 A23 1gjd
11421
-7.12 6 6 6 6 pH 7.4, EDTA ChemBio2000,7




164 A24 1gja
7136
-7.39 3.8 3.8 3.8 3.8 pH 7.4, EDTA ChemBio2000,8




165 A25 1ejn
AGB
-7.662 2.4 2.4 2.4 2.4
PNAS2000,97




166 A26 1f5l
amiloride
-7.193 5.3 5.3 5.3
JMB2000,301





A27 1fv9





?





167 A28 1f92
UKI-1D
-8.445 0.64 0.64 0.64
JMB2000,301




168 A29 1sqa
UI1/23b
-12.55 0.00062 0.00062 0.62 0.00062
BioorgMEDChem2004,14




169 A30 1sqo
UI2/2
-10.17 0.035 0.035 0.035 0.035
BioorgMEDChem2004,15




170 A31 1sqt
12b
-8.454 0.63 0.63 0.63 0.63
BioorgMEDChem2004,16




171 A32 1owd
56a
-9.324 0.145 0.0063 6.3 0.0063
JMC2004,47




172 A33 1owe
6
-8.453 0.631 0.631 0.631 0.631
JMC2004,48




173 A34 1owh
25
-10.09 0.04 0.04 0.631 0.04
JMC2004,49




174 A35 1owi
34d
-9.521 0.104 0.104 0.104
JMC2004,50




175 A36 1owj
43a
-9.979 0.048 0.048 0.048
JMC2004,51




176 A37 1owk
47a
-10.4 0.0235 0.035 0.035
JMC2004,52




177 A38 1u6q
19a
-8.021 1.31 1.31 1.31
BioorgMedChem2005,15




178 A39 1vja
26
-10.5 0.02 0.02 0.02 0.02
JBC2004,279




179 A40 1vj9
27
-10.3 0.028 0.028 0.028 0.028
JBC2004,280




180 A41 1sc8
1
-6.817 10 0.036 0.036 0.036
JBC2004,281





A42 1gj9
134


0.011 ?




















Katz Katz JMB2004,344











Katz Katz JMB2003,93













Katz Verner JMC2001,44













Katz Katz JMB2001,307











Katz Katz JACS













Katz Katz ChemBio2001,8











Katz Spencer BioorgMedChem2002,12











Strzebecher Zeslawska JMB2000,301











Katz Katz ChemBio2000,7











Strzebecher Sperl PNAS2000,97











Wendt Wendt BioorgMEDChem2004,14











Wendt Wendt JMC2004,47













Wendt Bruncko BioorgMedChem2005,15











Strzebecher Schweinitz JBC2004,281