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 T86528 Target Info
Target Name Geranyltranstransferase (FDPS)
Synonyms KIAA1293; Geranylgeranyl pyrophosphate synthase; Geranylgeranyl diphosphate synthase; GGPS1; GGPPSase; GGPP synthase; Farnesyltranstransferase; Farnesyl pyrophosphate synthase; Farnesyl diphosphate synthase; FPS protein; FPP synthase; Dimethylallyltranstransferase; (2E,6E)-farnesyl diphosphate synthase
Target Type Successful Target
Gene Name FDPS
Biochemical Class Alkyl aryl transferase
UniProt ID
FPPS_HUMAN
Ligand General Information  Top
Ligand Name ({[6-(4-Methylphenyl)thieno[2,3-D]pyrimidin-4-Yl]amino}methanediyl)bis(Phosphonic Acid) Ligand Info
Canonical SMILES CC1=CC=C(C=C1)C2=CC3=C(N=CN=C3S2)NC(P(=O)(O)O)P(=O)(O)O
InChI 1S/C14H15N3O6P2S/c1-8-2-4-9(5-3-8)11-6-10-12(15-7-16-13(10)26-11)17-14(24(18,19)20)25(21,22)23/h2-7,14H,1H3,(H,15,16,17)(H2,18,19,20)(H2,21,22,23)
InChIKey SFWLGYOMOJOLFV-UHFFFAOYSA-N
PubChem Compound ID 71583208
Drug Binding Sites of Target  Top
PDB ID: 4LPG      Crystal structure of human FPPS in complex with CL01131
Method X-ray diffraction Resolution 2.35 Å Mutation No [1]
PDB Sequence
DVYAQEKQDF
17
VQHFSQIVRV
27
LTEEMGHPEI
38
GDAIARLKEV
48
LEYNAIGGKY
58

NRGLTVVVAF
68
RELVEPRKQD
78
ADSLQRAWTV
88
GWCVELLQAF
98
FLVADDIMDS
108

SLTRRGQICW
118
YQKPGVGLDA
128
INDANLLEAC
138
IYRLLKLYCR
148
EQPYYLNLIE
158

LFLQSSYQTE
168
IGQTLDLLTA
178
PQGNVDLVRF
188
TEKRYKSIVK
198
YKTAFYSFYL
208

PIAAAMYMAG
218
IDGEKEHANA
228
KKILLEMGEF
238
FQIQDDYLDL
248
FGDPSVTGKI
258

GTDIQDNKCS
268
WLVVQCLQRA
278
TPEQYQILKE
288
NYGQKEAEKV
298
ARVKALYEEL
308

DLPAVFLQYE
318
EDSYSHIMAL
328
IEQYAAPLPP
338
AVFLGLARKI
348
Y
Residue
Distance (Å)
TYR10
4.613
LYS57
3.022
ASN59
3.239
ARG60
4.053
THR63
3.580
SER205
3.188
PHE206
3.794
Residue
Distance (Å)
PRO209
4.793
PHE239
3.748
ASP243
4.198
LEU344
3.786
LYS347
3.695
ILE348
4.286
PDB ID: 4JVJ      Crystal structure of human FPPS in complex with magnesium, CL01131, and sulfate
Method X-ray diffraction Resolution 2.80 Å Mutation No [2]
PDB Sequence
DVYAQEKQDF
17
VQHFSQIVRV
27
LTEDEMGHPE
37
IGDAIARLKE
47
VLEYNAIGGK
57

YNRGLTVVVA
67
FRELVEPRKQ
77
DADSLQRAWT
87
VGWCVELLQA
97
FFLVADDIMD
107

SSLTRRGQIC
117
WYQKPGVGLD
127
AINDANLLEA
137
CIYRLLKLYC
147
REQPYYLNLI
157

ELFLQSSYQT
167
EIGQTLDLLT
177
APQGNVDLVR
187
FTEKRYKSIV
197
KYKTAFYSFY
207

LPIAAAMYMA
217
GIDGEKEHAN
227
AKKILLEMGE
237
FFQIQDDYLD
247
LFGDPSVTGK
257

IGTDIQDNKC
267
SWLVVQCLQR
277
ATPEQYQILK
287
ENYGQKEAEK
297
VARVKALYEE
307

LDLPAVFLQY
317
EEDSYSHIMA
327
LIEQYAAPLP
337
PAVFLGLARK
347
IYK
Residue
Distance (Å)
PHE99
3.102
LEU100
4.601
ALA102
4.519
ASP103
2.796
MET106
3.766
ASP107
3.022
ARG112
2.382
THR167
3.283
GLU168
4.528
GLN171
2.910
ASP174
4.547
Residue
Distance (Å)
LYS200
2.722
THR201
3.116
TYR204
3.355
SER205
4.798
GLN240
3.137
ASP243
2.855
ASP244
4.251
LYS257
3.957
ASP261
4.692
LYS266
4.550
References  Top
REF 1 Multistage screening reveals chameleon ligands of the human farnesyl pyrophosphate synthase: implications to drug discovery for neurodegenerative diseases. J Med Chem. 2014 Jul 10;57(13):5764-76.
REF 2 Thienopyrimidine bisphosphonate (ThPBP) inhibitors of the human farnesyl pyrophosphate synthase: optimization and characterization of the mode of inhibition. J Med Chem. 2013 Oct 24;56(20):7939-50.

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