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 [(1r)-1-{[6-(3-Chloro-4-Methylphenyl)thieno[2,3-D]pyrimidin-4-Yl]amino}-2-(3-Fluorophenyl)ethyl]phosphonic Acid Ligand Info
Canonical SMILES CC1=C(C=C(C=C1)C2=CC3=C(N=CN=C3S2)NC(CC4=CC(=CC=C4)F)P(=O)(O)O)Cl
InChI 1S/C21H18ClFN3O3PS/c1-12-5-6-14(9-17(12)22)18-10-16-20(24-11-25-21(16)31-18)26-19(30(27,28)29)8-13-3-2-4-15(23)7-13/h2-7,9-11,19H,8H2,1H3,(H,24,25,26)(H2,27,28,29)/t19-/m1/s1
InChIKey ZSPBSSJYWQDARC-LJQANCHMSA-N
PubChem Compound ID 124220687
Drug Binding Sites of Target  Top
PDB ID: 6N83      Crystal structure of human FPPS in complex with an allosteric inhibitor YF-02037
Method X-ray diffraction Resolution 2.00 Å Mutation No [1]
PDB Sequence
SDVYAQEKQD
16
FVQHFSQIVR
26
VLTEGHPEIG
39
DAIARLKEVL
49
EYNAIGGKYN
59

RGLTVVVAFR
69
ELVEPRKQDA
79
DSLQRAWTVG
89
WCVELLQAFF
99
LVADDIMDSS
109

LTRRGQICWY
119
QKPGVGLDAI
129
NDANLLEACI
139
YRLLKLYCRE
149
QPYYLNLIEL
159

FLQSSYQTEI
169
GQTLDLLTAP
179
QGNVDLVRFT
189
EKRYKSIVKY
199
KTAFYSFYLP
209

IAAAMYMAGI
219
DGEKEHANAK
229
KILLEMGEFF
239
QIQDDYLDLF
249
GDPSVTGKIG
259

TDIQDNKCSW
269
LVVQCLQRAT
279
PEQYQILKEN
289
YGQKEAEKVA
299
RVKALYEELD
309

LPAVFLQYEE
319
DSYSHIMALI
329
EQYAAPLPPA
339
VFLGLARKIY
349
K
Residue
Distance (Å)
LYS57
3.224
ASN59
3.213
ARG60
3.548
THR63
3.716
SER205
3.457
PHE206
3.552
PHE238
4.408
PHE239
3.232
Residue
Distance (Å)
GLN242
2.450
ASP243
3.581
LEU246
4.030
VAL254
4.617
LEU344
3.737
LYS347
3.931
ILE348
3.643
LYS350
3.264
PDB ID: 5JV1      Crystal structure of human FPPS in complex with an allosteric inhibitor CL-08-066
Method X-ray diffraction Resolution 2.30 Å Mutation No [2]
PDB Sequence
VYAQEKQDFV
18
QHFSQIVRVL
28
TEHPEIGDAI
42
ARLKEVLEYN
52
AIGGKYNRGL
62

TVVVAFRELV
72
EPRKQDADSL
82
QRAWTVGWCV
92
ELLQAFFLVA
102
DDIMDSSLTR
112

RGQICWYQKP
122
GVGLDAINDA
132
NLLEACIYRL
142
LKLYCREQPY
152
YLNLIELFLQ
162

SSYQTEIGQT
172
LDLLTAPNVD
184
LVRFTEKRYK
194
SIVKYKTAFY
204
SFYLPIAAAM
214

YMAGIDGEKE
224
HANAKKILLE
234
MGEFFQIQDD
244
YLDLFGDPSV
254
TGKIGTDIQD
264

NKCSWLVVQC
274
LQRATPEQYQ
284
ILKENYGQKE
294
AEKVARVKAL
304
YEELDLPAVF
314

LQYEEDSYSH
324
IMALIEQYAA
334
PLPPAVFLGL
344
ARKIYK
Residue
Distance (Å)
TYR10
4.494
LYS57
3.677
ASN59
3.291
ARG60
3.660
THR63
3.917
SER205
3.259
PHE206
3.565
PHE238
4.452
PHE239
3.290
GLN242
2.595
ASP243
3.594
LEU246
4.153
LEU315
4.084
Residue
Distance (Å)
GLU318
3.835
GLU319
3.593
TYR322
3.255
MET326
3.494
LEU342
3.762
LEU344
3.578
ALA345
3.697
ARG346
3.545
LYS347
3.993
ILE348
3.691
TYR349
2.623
LYS350
2.729
References  Top
REF 1 Chirality-Driven Mode of Binding of Alpha-Aminophosphonic Acid-Based Allosteric Inhibitors of the Human Farnesyl Pyrophosphate Synthase (hFPPS). J Med Chem. 2019 Nov 14;62(21):9691-9702.
REF 2 Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase. J Med Chem. 2017 Mar 9;60(5):2119-2134.

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