Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Zoledronate | Ligand Info | |||
| Canonical SMILES | C1=CN(C=N1)CC(O)(P(=O)(O)O)P(=O)(O)O | ||||
| InChI | 1S/C5H10N2O7P2/c8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14) | ||||
| InChIKey | XRASPMIURGNCCH-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 68740 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4KFA Crystal structure of human farnesyl pyrophosphate synthase (t201a mutant) complexed with mg and zoledronate | ||||||
| Method | X-ray diffraction | Resolution | 1.98 Å | Mutation | Yes | [1] |
| PDB Sequence |
VYAQEKQDFV
18 QHFSQIVRVL28 TEHPEIGDAI42 ARLKEVLEYN52 AIGGKYNRGL62 TVVVAFRELV 72 EPRKQDADSL82 QRAWTVGWCV92 ELLQAFFLVA102 DDIMDSSLTR112 RGQICWYQKP 122 GVGLDAINDA132 NLLEACIYRL142 LKLYCREQPY152 YLNLIELFLQ162 SSYQTEIGQT 172 LDLLTAPQGN182 VDLVRFTEKR192 YKSIVKYKAA202 FYSFYLPIAA212 AMYMAGIDGE 222 KEHANAKKIL232 LEMGEFFQIQ242 DDYLDLFGDP252 SVTGKIGTDI262 QDNKCSWLVV 272 QCLQRATPEQ282 YQILKENYGQ292 KEAEKVARVK302 ALYEELDLPA312 VFLQYEEDSY 322 SHIMALIEQY332 AAPLPPAVFL342 GLARKIYK
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| PDB ID: 4KQ5 Crystal Structure of Human Farnesyl Pyrophosphate Synthase Mutant (Y204A) Complexed with Mg and Zoledronate | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [2] |
| PDB Sequence |
VYAQEKQDFV
18 QHFSQIVRVL28 TEDEMGHPEI38 GDAIARLKEV48 LEYNAIGGKY58 NRGLTVVVAF 68 RELVEPRKQD78 ADSLQRAWTV88 GWCVELLQAF98 FLVADDIMDS108 SLTRRGQICW 118 YQKPGVGLDA128 INDANLLEAC138 IYRLLKLYCR148 EQPYYLNLIE158 LFLQSSYQTE 168 IGQTLDLLTA178 PQGNVDLVRF188 TEKRYKSIVK198 YKTAFASFYL208 PIAAAMYMAG 218 IDGEKEHANA228 KKILLEMGEF238 FQIQDDYLDL248 FGDPSVTGKI258 GTDIQDNKCS 268 WLVVQCLQRA278 TPEQYQILKE288 NYGQKEAEKV298 ARVKALYEEL308 DLPAVFLQYE 318 EDSYSHIMAL328 IEQYAAPLPP338 AVFLGLARKI348 YK
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| PDB ID: 1ZW5 X-ray structure of Farnesyl diphosphate synthase protein | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [3] |
| PDB Sequence |
EKQDFVQHFS
36 QIVRVLTEDE46 HPEIGDAIAR58 LKEVLEYNAI68 GGKYNRGLTV78 VVAFRELVEP 88 RKQDADSLQR98 AWTVGWCVEL108 LQAFFLVADD118 IMDSSLTRRG128 QICWYQKPGV 138 GLDAINDANL148 LEACIYRLLK158 LYCREQPYYL168 NLIELFLQSS178 YQTEIGQTLD 188 LLTAPQGNVD198 LVRFTEKRYK208 SIVKYKTAFY218 SFYLPIAAAM228 YMAGIDGEKE 238 HANAKKILLE248 MGEFFQIQDD258 YLDLFGDPSV268 TGKIGTDIQD278 NKCSWLVVQC 288 LQRATPEQYQ298 ILKENYGQKE308 AEKVARVKAL318 YEELDLPAVF328 LQYEEDSYSH 338 IMALIEQYAA348 PLPPAVFLGL358 ARKIYKRRK
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| PDB ID: 3N45 Human FPPS complex with FBS_04 and zoledronic acid/MG2+ | ||||||
| Method | X-ray diffraction | Resolution | 1.88 Å | Mutation | No | [4] |
| PDB Sequence |
DVYAQEKQDF
17 VQHFSQIVRV27 LTEDEMGHPE37 IGDAIARLKE47 VLEYNAIGGK57 YNRGLTVVVA 67 FRELVEPRKQ77 DADSLQRAWT87 VGWCVELLQA97 FFLVADDIMD107 SSLTRRGQIC 117 WYQKPGVGLD127 AINDANLLEA137 CIYRLLKLYC147 REQPYYLNLI157 ELFLQSSYQT 167 EIGQTLDLLT177 APQGNVDLVR187 FTEKRYKSIV197 KYKTAFYSFY207 LPIAAAMYMA 217 GIDGEKEHAN227 AKKILLEMGE237 FFQIQDDYLD247 LFGDPSVTGK257 IGTDIQDNKC 267 SWLVVQCLQR277 ATPEQYQILK287 ENYGQKEAEK297 VARVKALYEE307 LDLPAVFLQY 317 EEDSYSHIMA327 LIEQYAAPLP337 PAVFLGLARK347 IYK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZOL or .ZOL2 or .ZOL3 or :3ZOL;style chemicals stick;color identity;select .F:100 or .F:103 or .F:104 or .F:107 or .F:112 or .F:167 or .F:171 or .F:174 or .F:200 or .F:201 or .F:204 or .F:240 or .F:243 or .F:244 or .F:247 or .F:257 or .F:261; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2F9K Crystal structure of human FPPS in complex with Zoledronate and Zn2+ | ||||||
| Method | X-ray diffraction | Resolution | 2.06 Å | Mutation | No | [5] |
| PDB Sequence |
DVYAQEKQDF
17 VQHFSQIVRV27 LTEDEMGHPE37 IGDAIARLKE47 VLEYNAIGGK57 YNRGLTVVVA 67 FRELVEPRKQ77 DADSLQRAWT87 VGWCVELLQA97 FFLVADDIMD107 SSLTRRGQIC 117 WYQKPGVGLD127 AINDANLLEA137 CIYRLLKLYC147 REQPYYLNLI157 ELFLQSSYQT 167 EIGQTLDLLT177 APQGNVDLVR187 FTEKRYKSIV197 KYKTAFYSFY207 LPIAAAMYMA 217 GIDGEKEHAN227 AKKILLEMGE237 FFQIQDDYLD247 LFGDPSVTGK257 IGTDIQDNKC 267 SWLVVQCLQR277 ATPEQYQILK287 ENYGQKEAEK297 VARVKALYEE307 LDLPAVFLQY 317 EEDSYSHIMA327 LIEQYAAPLP337 PAVFLGLARK347 IYK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZOL or .ZOL2 or .ZOL3 or :3ZOL;style chemicals stick;color identity;select .F:100 or .F:103 or .F:104 or .F:107 or .F:112 or .F:167 or .F:171 or .F:174 or .F:200 or .F:201 or .F:204 or .F:240 or .F:243 or .F:244 or .F:247 or .F:257 or .F:261; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2F8C Crystal structure of FPPS in complex with Zoledronate | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [5] |
| PDB Sequence |
DVYAQEKQDF
17 VQHFSQIVRV27 LTEDEMGHPE37 IGDAIARLKE47 VLEYNAIGGK57 YNRGLTVVVA 67 FRELVEPRKQ77 DADSLQRAWT87 VGWCVELLQA97 FFLVADDIMD107 SSLTRRGQIC 117 WYQKPGVGLD127 AINDANLLEA137 CIYRLLKLYC147 REQPYYLNLI157 ELFLQSSYQT 167 EIGQTLDLLT177 APQGNVDLVR187 FTEKRYKSIV197 KYKTAFYSFY207 LPIAAAMYMA 217 GIDGEKEHAN227 AKKILLEMGE237 FFQIQDDYLD247 LFGDPSVTGK257 IGTDIQDNKC 267 SWLVVQCLQR277 ATPEQYQILK287 ENYGQKEAEK297 VARVKALYEE307 LDLPAVFLQY 317 EEDSYSHIMA327 LIEQYAAPLP337 PAVFLGLARK347 IYK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZOL or .ZOL2 or .ZOL3 or :3ZOL;style chemicals stick;color identity;select .F:100 or .F:103 or .F:104 or .F:107 or .F:109 or .F:112 or .F:171 or .F:174 or .F:200 or .F:201 or .F:204 or .F:240 or .F:243 or .F:244 or .F:247 or .F:257 or .F:261; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3N46 Human FPPS complex with NOV_980 and zoledronic acid/MG2+ | ||||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [4] |
| PDB Sequence |
DVYAQEKQDF
17 VQHFSQIVRV27 LTEDEMGHPE37 IGDAIARLKE47 VLEYNAIGGK57 YNRGLTVVVA 67 FRELVEPRKQ77 DADSLQRAWT87 VGWCVELLQA97 FFLVADDIMD107 SSLTRRGQIC 117 WYQKPGVGLD127 AINDANLLEA137 CIYRLLKLYC147 REQPYYLNLI157 ELFLQSSYQT 167 EIGQTLDLLT177 APQGNVDLVR187 FTEKRYKSIV197 KYKTAFYSFY207 LPIAAAMYMA 217 GIDGEKEHAN227 AKKILLEMGE237 FFQIQDDYLD247 LFGDPSVTGK257 IGTDIQDNKC 267 SWLVVQCLQR277 ATPEQYQILK287 ENYGQKEAEK297 VARVKALYEE307 LDLPAVFLQY 317 EEDSYSHIMA327 LIEQYAAPLP337 PAVFLGLARK347 IYK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZOL or .ZOL2 or .ZOL3 or :3ZOL;style chemicals stick;color identity;select .F:100 or .F:103 or .F:104 or .F:107 or .F:109 or .F:112 or .F:167 or .F:171 or .F:174 or .F:200 or .F:201 or .F:204 or .F:240 or .F:243 or .F:244 or .F:247 or .F:257 or .F:261 or .F:266; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2F8Z Crystal structure of human FPPS in complex with zoledronate and isopentenyl diphosphate | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [5] |
| PDB Sequence |
DVYAQEKQDF
17 VQHFSQIVRV27 LTEDEMGHPE37 IGDAIARLKE47 VLEYNAIGGK57 YNRGLTVVVA 67 FRELVEPRKQ77 DADSLQRAWT87 VGWCVELLQA97 FFLVADDIMD107 SSLTRRGQIC 117 WYQKPGVGLD127 AINDANLLEA137 CIYRLLKLYC147 REQPYYLNLI157 ELFLQSSYQT 167 EIGQTLDLLT177 APQGNVDLVR187 FTEKRYKSIV197 KYKTAFYSFY207 LPIAAAMYMA 217 GIDGEKEHAN227 AKKILLEMGE237 FFQIQDDYLD247 LFGDPSVTGK257 IGTDIQDNKC 267 SWLVVQCLQR277 ATPEQYQILK287 ENYGQKEAEK297 VARVKALYEE307 LDLPAVFLQY 317 EEDSYSHIMA327 LIEQYAAPLP337 PAVFLGLARK347 IYKRRK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZOL or .ZOL2 or .ZOL3 or :3ZOL;style chemicals stick;color identity;select .F:100 or .F:103 or .F:104 or .F:107 or .F:109 or .F:112 or .F:171 or .F:174 or .F:200 or .F:201 or .F:204 or .F:240 or .F:243 or .F:244 or .F:247 or .F:257 or .F:261; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4P0W Human farnesyl diphosphate synthase in complex with Arenarone and zoledronate | ||||||
| Method | X-ray diffraction | Resolution | 2.41 Å | Mutation | No | [6] |
| PDB Sequence |
DVYAQEKQDF
17 VQHFSQIVRV27 LTEDEMGHPE37 IGDAIARLKE47 VLEYNAIGGK57 YNRGLTVVVA 67 FRELVEPRKQ77 DADSLQRAWT87 VGWCVELLQA97 FFLVADDIMD107 SSLTRRGQIC 117 WYQKPGVGLD127 AINDANLLEA137 CIYRLLKLYC147 REQPYYLNLI157 ELFLQSSYQT 167 EIGQTLDLLT177 APQGNVDLVR187 FTEKRYKSIV197 KYKTAFYSFY207 LPIAAAMYMA 217 GIDGEKEHAN227 AKKILLEMGE237 FFQIQDDYLD247 LFGDPSVTGK257 IGTDIQDNKC 267 SWLVVQCLQR277 ATPEQYQILK287 ENYGQKEAEK297 VARVKALYEE307 LDLPAVFLQY 317 EEDSYSHIMA327 LIEQYAAPLP337 PAVFLGLARK347 IYKRRK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZOL or .ZOL2 or .ZOL3 or :3ZOL;style chemicals stick;color identity;select .A:100 or .A:103 or .A:104 or .A:107 or .A:112 or .A:171 or .A:174 or .A:200 or .A:201 or .A:204 or .A:240 or .A:243 or .A:244 or .A:257 or .A:261; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4P0V Crystal structure of human farnesyl diphosphoate synthase in complex with zoledronate and taxodione | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [6] |
| PDB Sequence |
DVYAQEKQDF
17 VQHFSQIVRV27 LTEDEMGHPE37 IGDAIARLKE47 VLEYNAIGGK57 YNRGLTVVVA 67 FRELVEPRKQ77 DADSLQRAWT87 VGWCVELLQA97 FFLVADDIMD107 SSLTRRGQIC 117 WYQKPGVGLD127 AINDANLLEA137 CIYRLLKLYC147 REQPYYLNLI157 ELFLQSSYQT 167 EIGQTLDLLT177 APQGNVDLVR187 FTEKRYKSIV197 KYKTAFYSFY207 LPIAAAMYMA 217 GIDGEKEHAN227 AKKILLEMGE237 FFQIQDDYLD247 LFGDPSVTGK257 IGTDIQDNKC 267 SWLVVQCLQR277 ATPEQYQILK287 ENYGQKEAEK297 VARVKALYEE307 LDLPAVFLQY 317 EEDSYSHIMA327 LIEQYAAPLP337 PAVFLGLARK347 IYKRRK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZOL or .ZOL2 or .ZOL3 or :3ZOL;style chemicals stick;color identity;select .A:100 or .A:103 or .A:104 or .A:107 or .A:112 or .A:171 or .A:174 or .A:200 or .A:201 or .A:204 or .A:240 or .A:243 or .A:244 or .A:257 or .A:261; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structure of human farnesyl pyrophosphate synthase (t201a mutant) complexed with mg and zoledronate | ||||
| REF 2 | Crystal Structure of Human Farnesyl Pyrophosphate Synthase Mutant (Y204A) Complexed with Mg and Zoledronate | ||||
| REF 3 | The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7829-34. | ||||
| REF 4 | Allosteric non-bisphosphonate FPPS inhibitors identified by fragment-based discovery. Nat Chem Biol. 2010 Sep;6(9):660-6. | ||||
| REF 5 | Structural basis for the exceptional in vivo efficacy of bisphosphonate drugs. ChemMedChem. 2006 Feb;1(2):267-73. | ||||
| REF 6 | Taxodione and arenarone inhibit farnesyl diphosphate synthase by binding to the isopentenyl diphosphate site. Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):E2530-9. | ||||
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