Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T71081 Target Info
Target Name GTPase HRas (HRAS)
Synonyms p21ras; cHras; c-H-ras; Transforming protein p21; HaRas; Ha-Ras; H-Ras-1; GTPase HRas, Nterminally processed
Target Type Literature-reported Target
Gene Name HRAS
Biochemical Class Small GTPase
UniProt ID
RASH_HUMAN
Ligand General Information  Top
Ligand Name Guanosine-5'-Triphosphate Ligand Info
Canonical SMILES C1=NC2=C(N1C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O)O)N=C(NC2=O)N
InChI 1S/C10H16N5O14P3/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(27-9)1-26-31(22,23)29-32(24,25)28-30(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1
InChIKey XKMLYUALXHKNFT-UUOKFMHZSA-N
PubChem Compound ID 135398633
Drug Binding Sites of Target  Top
PDB ID: 2C5L      Structure of PLC epsilon Ras association domain with hRas
Method X-ray diffraction Resolution 1.90 Å Mutation Yes [1]
PDB Sequence
MTEYKLVVVG
10
AVGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHQYREQI
100

KRVKDSDDVP
110
MVLVGNKCDL
120
AARTVESRQA
130
QDLARSYGIP
140
YIETSAKTRQ
150

GVEDAFYTLV
160
REIRQH
Residue
Distance (Å)
GLY10
4.789
ALA11
3.887
VAL12
3.605
GLY13
3.085
VAL14
3.235
GLY15
3.154
LYS16
2.670
SER17
2.950
ALA18
2.821
PHE28
3.259
VAL29
2.758
ASP30
2.948
GLU31
3.820
TYR32
2.557
ASP33
4.474
PRO34
3.428
Residue
Distance (Å)
THR35
2.979
ASP57
4.713
THR58
4.182
ALA59
4.094
GLY60
2.914
GLN61
4.341
ASN116
3.196
LYS117
3.344
CYS118
4.838
ASP119
2.714
LEU120
3.370
THR144
4.661
SER145
3.477
ALA146
2.977
LYS147
3.607
PDB ID: 4K81      Crystal structure of the Grb14 RA and PH domains in complex with GTP-loaded H-Ras
Method X-ray diffraction Resolution 2.40 Å Mutation Yes [2]
PDB Sequence
GAMGSMTEYK
5
LVVVGAVGVG
15
KSALTIQLIQ
25
NHFVDEYDPT
35
IEDSYRKQVV
45

IDGETCLLDI
55
LDTAGQEEYS
65
AMRDQYMRTG
75
EGFLCVFAIN
85
NTKSFEDIHQ
95

YREQIKRVKD
105
SDDVPMVLVG
115
NKCDLAARTV
125
ESRQAQDLAR
135
SYGIPYIETS
145

AKTRQGVEDA
155
FYTLVREIRQ
165
H
Residue
Distance (Å)
GLY10
4.591
ALA11
3.730
VAL12
4.110
GLY13
3.084
VAL14
3.080
GLY15
3.016
LYS16
2.634
SER17
3.093
ALA18
3.005
PHE28
3.491
VAL29
2.746
ASP30
2.830
GLU31
3.655
TYR32
2.682
ASP33
4.160
PRO34
4.021
Residue
Distance (Å)
THR35
2.611
ASP57
4.463
THR58
3.795
ALA59
4.034
GLY60
3.120
GLN61
4.756
ASN116
3.279
LYS117
3.098
CYS118
4.812
ASP119
2.707
LEU120
3.513
THR144
4.610
SER145
3.459
ALA146
2.788
LYS147
3.563
PDB ID: 2CL7      CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GTP
Method X-ray diffraction Resolution 1.25 Å Mutation Yes [3]
PDB Sequence
MTEYKLVVVG
10
AGGVGKSALT
20
IQLIQNHFVD
30
ECDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHQYREQI
100

KRVKDSDDVP
110
MVLVGNKSDL
120
AARTVESRQA
130
QDLARSYGIP
140
YIETSAKTRQ
150

GVEDAFYTLV
160
REIRQH
Residue
Distance (Å)
GLY10
4.921
ALA11
3.730
GLY12
3.180
GLY13
2.717
VAL14
3.159
GLY15
3.056
LYS16
2.487
SER17
3.309
ALA18
3.146
PHE28
3.211
VAL29
2.983
ASP30
3.087
GLU31
4.860
ASP33
4.418
PRO34
4.553
Residue
Distance (Å)
THR35
2.883
ASP57
4.652
THR58
4.377
ALA59
3.728
GLY60
2.639
ASN116
2.971
LYS117
3.105
SER118
4.506
ASP119
2.694
LEU120
3.491
THR144
4.442
SER145
3.464
ALA146
3.015
LYS147
3.779
PDB ID: 2CLC      CRYSTAL STRUCTURE ANALYSIS OF A FLUORESCENT FORM OF H-RAS P21 IN COMPLEX WITH GTP (2)
Method X-ray diffraction Resolution 1.30 Å Mutation Yes [3]
PDB Sequence
MTEYKLVVVG
10
AGGVGKSALT
20
IQLIQNHFVD
30
ECDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHQYREQI
100

KRVKDSDDVP
110
MVLVGNKSDL
120
AARTVESRQA
130
QDLARSYGIP
140
YIETSAKTRQ
150

GVEDAFYTLV
160
REIRQH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTP or .GTP2 or .GTP3 or :3GTP;style chemicals stick;color identity;select .X:10 or .X:11 or .X:12 or .X:13 or .X:14 or .X:15 or .X:16 or .X:17 or .X:18 or .X:28 or .X:29 or .X:30 or .X:31 or .X:33 or .X:34 or .X:35 or .X:57 or .X:58 or .X:59 or .X:60 or .X:116 or .X:117 or .X:118 or .X:119 or .X:120 or .X:144 or .X:145 or .X:146 or .X:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLY10
4.815
ALA11
3.748
GLY12
3.202
GLY13
2.783
VAL14
3.177
GLY15
3.076
LYS16
2.466
SER17
3.189
ALA18
3.113
PHE28
3.416
VAL29
3.099
ASP30
3.118
GLU31
4.410
ASP33
4.312
PRO34
4.098
Residue
Distance (Å)
THR35
3.051
ASP57
4.586
THR58
4.014
ALA59
3.736
GLY60
2.624
ASN116
2.981
LYS117
3.169
SER118
4.688
ASP119
2.752
LEU120
3.455
THR144
4.572
SER145
3.602
ALA146
3.051
LYS147
3.863
PDB ID: 1QRA      STRUCTURE OF P21RAS IN COMPLEX WITH GTP AT 100 K
Method X-ray diffraction Resolution 1.60 Å Mutation No [4]
PDB Sequence
MTEYKLVVVG
10
AGGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHQYREQI
100

KRVKDSDDVP
110
MVLVGNKCDL
120
AARTVESRQA
130
QDLARSYGIP
140
YIETSAKTRQ
150

GVEDAFYTLV
160
REIRQH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTP or .GTP2 or .GTP3 or :3GTP;style chemicals stick;color identity;select .A:10 or .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:33 or .A:34 or .A:35 or .A:57 or .A:58 or .A:59 or .A:60 or .A:61 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLY10
4.919
ALA11
3.812
GLY12
3.526
GLY13
3.056
VAL14
3.199
GLY15
2.983
LYS16
2.661
SER17
2.868
ALA18
2.806
PHE28
3.302
VAL29
2.635
ASP30
3.010
GLU31
3.714
TYR32
4.582
ASP33
4.321
PRO34
3.587
Residue
Distance (Å)
THR35
2.910
ASP57
4.656
THR58
4.094
ALA59
3.986
GLY60
2.862
GLN61
4.814
ASN116
3.161
LYS117
3.154
CYS118
4.733
ASP119
2.764
LEU120
3.568
THR144
4.581
SER145
3.417
ALA146
2.796
LYS147
3.586
PDB ID: 2UZI      Crystal structure of HRAS(G12V) - anti-RAS Fv complex
Method X-ray diffraction Resolution 2.00 Å Mutation Yes [5]
PDB Sequence
MTEYKLVVVG
10
AVGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHQYREQI
100

KRVKDSDDVP
110
MVLVGNKCDL
120
AARTVESRQA
130
QDLARSYGIP
140
YIETSAKTRQ
150

GVEDAFYTLV
160
REIRQH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTP or .GTP2 or .GTP3 or :3GTP;style chemicals stick;color identity;select .R:11 or .R:12 or .R:13 or .R:14 or .R:15 or .R:16 or .R:17 or .R:18 or .R:19 or .R:28 or .R:29 or .R:30 or .R:31 or .R:32 or .R:33 or .R:34 or .R:35 or .R:57 or .R:58 or .R:59 or .R:60 or .R:61 or .R:116 or .R:117 or .R:119 or .R:120 or .R:144 or .R:145 or .R:146 or .R:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.732
VAL12
3.913
GLY13
3.065
VAL14
3.383
GLY15
3.085
LYS16
2.737
SER17
2.937
ALA18
2.730
LEU19
4.989
PHE28
3.338
VAL29
2.464
ASP30
3.123
GLU31
3.683
TYR32
2.581
ASP33
4.172
Residue
Distance (Å)
PRO34
3.671
THR35
2.822
ASP57
4.552
THR58
3.803
ALA59
3.819
GLY60
2.742
GLN61
4.503
ASN116
3.195
LYS117
3.211
ASP119
2.761
LEU120
3.705
THR144
4.709
SER145
3.555
ALA146
2.752
LYS147
3.531
PDB ID: 1NVU      Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [6]
PDB Sequence
MTEYKLVVVG
10
AGGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTGG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHQYREQI
100

KRVKDSDDVP
110
MVLVGNKCDL
120
AARTVESRQA
130
QDLARSYGIP
140
YIETSAKTRQ
150

GVEDAFYTLV
160
REIRQH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTP or .GTP2 or .GTP3 or :3GTP;style chemicals stick;color identity;select .Q:10 or .Q:11 or .Q:12 or .Q:13 or .Q:14 or .Q:15 or .Q:16 or .Q:17 or .Q:18 or .Q:28 or .Q:29 or .Q:30 or .Q:31 or .Q:32 or .Q:33 or .Q:34 or .Q:35 or .Q:57 or .Q:58 or .Q:59 or .Q:60 or .Q:62 or .Q:116 or .Q:117 or .Q:118 or .Q:119 or .Q:120 or .Q:144 or .Q:145 or .Q:146 or .Q:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLY10
4.783
ALA11
3.829
GLY12
3.200
GLY13
2.828
VAL14
3.202
GLY15
2.977
LYS16
2.712
SER17
3.076
ALA18
2.880
PHE28
3.393
VAL29
2.624
ASP30
2.972
GLU31
3.954
TYR32
2.493
ASP33
4.471
PRO34
3.497
Residue
Distance (Å)
THR35
2.758
ASP57
4.706
THR58
4.232
GLY59
3.713
GLY60
2.714
GLU62
3.446
ASN116
3.219
LYS117
3.237
CYS118
4.836
ASP119
2.612
LEU120
3.469
THR144
4.568
SER145
3.259
ALA146
2.781
LYS147
3.569
PDB ID: 521P      THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES
Method X-ray diffraction Resolution 2.60 Å Mutation Yes [7]
PDB Sequence
MTEYKLVVVG
10
AVGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTTG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHQYREQI
100

KRVKDSDDVP
110
MVLVGNKCDL
120
AARTVESRQA
130
QDLARSYGIP
140
YIETSAKTRQ
150

GVEDAFYTLV
160
REIRQH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTP or .GTP2 or .GTP3 or :3GTP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:33 or .A:34 or .A:35 or .A:57 or .A:58 or .A:59 or .A:60 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.517
VAL12
3.614
GLY13
3.250
VAL14
3.478
GLY15
3.230
LYS16
2.772
SER17
3.027
ALA18
2.763
PHE28
3.166
VAL29
2.697
ASP30
3.204
GLU31
4.463
TYR32
4.420
ASP33
4.553
PRO34
3.060
Residue
Distance (Å)
THR35
2.882
ASP57
4.535
THR58
4.033
THR59
4.146
GLY60
4.492
ASN116
3.593
LYS117
2.672
CYS118
4.888
ASP119
3.446
LEU120
3.812
THR144
4.704
SER145
3.657
ALA146
2.863
LYS147
3.551
PDB ID: 2VH5      CRYSTAL STRUCTURE OF HRAS(G12V) - ANTI-RAS FV (disulfide free mutant) COMPLEX
Method X-ray diffraction Resolution 2.70 Å Mutation Yes [8]
PDB Sequence
MTEYKLVVVG
10
AVGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHQYREQI
100

KRVKDSDDVP
110
MVLVGNKCDL
120
AARTVESRQA
130
QDLARSYGIP
140
YIETSAKTRQ
150

GVEDAFYTLV
160
REIRQH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTP or .GTP2 or .GTP3 or :3GTP;style chemicals stick;color identity;select .R:10 or .R:11 or .R:12 or .R:13 or .R:14 or .R:15 or .R:16 or .R:17 or .R:18 or .R:28 or .R:29 or .R:30 or .R:31 or .R:32 or .R:33 or .R:34 or .R:35 or .R:57 or .R:58 or .R:59 or .R:60 or .R:61 or .R:116 or .R:117 or .R:119 or .R:120 or .R:144 or .R:145 or .R:146 or .R:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLY10
4.949
ALA11
4.170
VAL12
3.986
GLY13
2.950
VAL14
3.469
GLY15
3.065
LYS16
2.785
SER17
2.614
ALA18
2.757
PHE28
3.630
VAL29
2.584
ASP30
2.818
GLU31
3.923
TYR32
2.914
ASP33
4.361
Residue
Distance (Å)
PRO34
3.628
THR35
2.508
ASP57
4.647
THR58
3.805
ALA59
3.846
GLY60
2.832
GLN61
4.621
ASN116
3.140
LYS117
3.078
ASP119
2.512
LEU120
3.455
THR144
4.590
SER145
3.469
ALA146
2.880
LYS147
3.708
PDB ID: 1PLK      CRYSTALLOGRAPHIC STUDIES ON P21H-RAS USING SYNCHROTRON LAUE METHOD: IMPROVEMENT OF CRYSTAL QUALITY AND MONITORING OF THE GTPASE REACTION AT DIFFERENT TIME POINTS
Method X-ray diffraction Resolution 2.80 Å Mutation No [9]
PDB Sequence
MTEYKLVVGG
13
GKSALTQIQN
26
HFVYDIEDSY
40
RKQVVIDGTC
51
LLDDTAGQEE
63

YSAMRDYMRT
74
GEGFVFAINN
86
TKSFEDIHQY
96
REQIKRKDSD
107
DVPMLVGNKC
118

DLAGRTVESR
128
QADARSYGIE
143
TSAKTRQVED
154
AFYLVREIRQ
165
H
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTP or .GTP2 or .GTP3 or :3GTP;style chemicals stick;color identity;select .A:13 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:32 or .A:33 or .A:58 or .A:59 or .A:60 or .A:61 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLY13
2.771
GLY15
3.132
LYS16
2.414
SER17
3.008
ALA18
2.975
PHE28
3.491
VAL29
3.274
TYR32
4.880
ASP33
3.216
THR58
3.276
ALA59
2.763
Residue
Distance (Å)
GLY60
2.925
GLN61
3.429
ASN116
3.130
LYS117
3.732
CYS118
4.951
ASP119
3.808
LEU120
3.109
THR144
4.793
SER145
4.257
ALA146
3.378
LYS147
3.124
PDB ID: 1NVX      Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS
Method X-ray diffraction Resolution 3.20 Å Mutation Yes [6]
PDB Sequence
MTEYKLVVVG
10
AGGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTGG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHQYREQI
100

KRVKDSDDVP
110
MVLVGNKCDL
120
AARTVESRQA
130
QDLARSYGIP
140
YIETSAKTRQ
150

GVEDAFYTLV
160
REIRQH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GTP or .GTP2 or .GTP3 or :3GTP;style chemicals stick;color identity;select .Q:10 or .Q:11 or .Q:12 or .Q:13 or .Q:14 or .Q:15 or .Q:16 or .Q:17 or .Q:18 or .Q:19 or .Q:28 or .Q:29 or .Q:30 or .Q:31 or .Q:32 or .Q:33 or .Q:34 or .Q:35 or .Q:57 or .Q:58 or .Q:59 or .Q:60 or .Q:62 or .Q:116 or .Q:117 or .Q:118 or .Q:119 or .Q:120 or .Q:144 or .Q:145 or .Q:146 or .Q:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLY10
4.614
ALA11
4.064
GLY12
3.220
GLY13
3.062
VAL14
3.487
GLY15
3.232
LYS16
2.700
SER17
2.667
ALA18
2.791
LEU19
4.920
PHE28
3.155
VAL29
2.916
ASP30
2.525
GLU31
3.435
TYR32
2.979
ASP33
4.551
Residue
Distance (Å)
PRO34
3.695
THR35
3.031
ASP57
4.500
THR58
3.645
GLY59
3.822
GLY60
2.751
GLU62
3.679
ASN116
2.914
LYS117
3.207
CYS118
4.848
ASP119
2.789
LEU120
4.047
THR144
4.385
SER145
3.435
ALA146
2.955
LYS147
3.175
References  Top
REF 1 Structural and mechanistic insights into ras association domains of phospholipase C epsilon. Mol Cell. 2006 Feb 17;21(4):495-507.
REF 2 Structural basis for the interaction of the adaptor protein grb14 with activated ras. PLoS One. 2013 Aug 13;8(8):e72473.
REF 3 A newly designed microspectrofluorometer for kinetic studies on protein crystals in combination with x-ray diffraction. Biophys J. 2006 Aug 1;91(3):981-92.
REF 4 The pre-hydrolysis state of p21(ras) in complex with GTP: new insights into the role of water molecules in the GTP hydrolysis reaction of ras-like proteins. Structure. 1999 Nov 15;7(11):1311-24.
REF 5 Tumour prevention by a single antibody domain targeting the interaction of signal transduction proteins with RAS. EMBO J. 2007 Jul 11;26(13):3250-9.
REF 6 Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS. Cell. 2003 Mar 7;112(5):685-95.
REF 7 Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules. Cell. 1990 Aug 10;62(3):539-48.
REF 8 Functional intracellular antibody fragments do not require invariant intra-domain disulfide bonds. J Mol Biol. 2008 Feb 22;376(3):749-57.
REF 9 Crystallographic studies on p21(H-ras) using the synchrotron Laue method: improvement of crystal quality and monitoring of the GTPase reaction at different time points. Acta Crystallogr D Biol Crystallogr. 1994 Jul 1;50(Pt 4):512-20.

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