Top Level Name

  ⌊ Superfamily (core) Isoprenoid Synthase Type I

    ⌊ Subgroup Polyprenyl Transferase Like

     ⌊ Family   private

  ⌊ FunctionalDomain farnesyl pyrophosphate synthase (ID 60098)

Superfamily Assignment Evidence Code(s) FSM PubMed:16684881
Family Assignment Evidence Code CFM PubMed:16684881
This entry was last updated onJune 10, 2017

References to Other Databases

Genbank

SpeciesGIAccessionProteome
Homo sapiens Taxon ID: 9606 209571582 NP_001129293.1 (RefSeq) PRP URP
Homo sapiens Taxon ID: 9606 4503685 NP_001995.1 (RefSeq) PRP URP
Pan paniscus Taxon ID: 9597 675740941 XP_008968430.1 (RefSeq) URP
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Uniprot

Protein NameAccessionEC Number Identifier
Farnesyl pyrophosphate synthase P14324 2.5.1.10 FPPS_HUMAN (Swiss-Prot)

Sequence

Length of Enzyme (full-length): 419 | Length of Functional Domain: 347

1       10        20        30        40        50        60

MPLSRWLRSVGVFLLPAPYWAPRERWLGSLRRPSLVHGYPVLAWHSARCWCQAWTEEPRA
LCSSLRMNGDQNSDVYAQEKQDFVQHFSQIVRVLTEDEMGHPEIGDAIARLKEVLEYNAI
GGKYNRGLTVVVAFRELVEPRKQDADSLQRAWTVGWCVELLQAFFLVADDIMDSSLTRRG
QICWYQKPGVGLDAINDANLLEACIYRLLKLYCREQPYYLNLIELFLQSSYQTEIGQTLD
LLTAPQGNVDLVRFTEKRYKSIVKYKTAFYSFYLPIAAAMYMAGIDGEKEHANAKKILLE
MGEFFQIQDDYLDLFGDPSVTGKIGTDIQDNKCSWLVVQCLQRATPEQYQILKENYGQKE
AEKVARVKALYEELDLPAVFLQYEEDSYSHIMALIEQYAAPLPPAVFLGLARKIYKRRK
This shows the full-length sequence of the enzyme. The region of the functional domain is highlighted in black letters, while the residual residues are shown in grey. The Superfamily domain, when present, is shown using underlining. In many cases the functional domain is the full-length sequence.
Conserved catalytic residues (as determined by automated alignment to family, subgroup, or superfamily HMMs) are shown with teal highlighting . Conserved catalytic residues which do not matched the Conserved Alignment Residue are shown with maroon highlighting . Information regarding their function can be found in the Conserved Residues section below.
FASTA formatted full-length sequence.
BLAST this sequence against SFLD.
Scan SFLD-HMMs with this sequence.

Conserved Residues
Superfamily CAR This EFD conserves 3/3 Superfamily-specific Conserved Alignment Residues.
Position Amino Acid Location Function Role Evidence Code Reference
169 Asp (D) side chain None --
173 Asp (D) side chain None --
309 Asp (D) side chain None --
Subgroup CAR This EFD conserves 9/9 Subgroup-specific Conserved Alignment Residues.
Position Amino Acid Location Function Role Evidence Code Reference
123 Lys (K) side chain Stabilizes fully closed conformation via electrostatic interaction with C-terminal carboxylate of IPP electrostatic stabiliser -- spectator ICS PubMed:16892359
169 Asp (D) side chain Metal ligand metal ligand -- binding ICS PubMed:21562622
170 Asp (D) side chain None -- ISS
173 Asp (D) side chain Metal ligand; Stabilizes partially closed conformation via electrostatic interaction with K330 electrostatic stabiliser -- spectator,
metal ligand -- binding 		ICS PubMed:16892359
178 Arg (R) side chain Hydrogen bonds to substrate diphosphate electrostatic stabiliser -- spectator ICS PubMed:21562622
240 Asp (D) side chain Stabilizes partially closed conformation via electrostatic interactions with K330 electrostatic stabiliser -- spectator ICS PubMed:16892359
266 Lys (K) side chain Hydrogen bonds to substrate diphosphate electrostatic stabiliser -- spectator ICS PubMed:21562622
309 Asp (D) side chain Metal ligand metal ligand -- binding ICS PubMed:21562622
310 Asp (D) side chain Metal ligand (via water) metal ligand -- binding ICS PubMed:21562622

Structures

PDB ID Title Molecule Name Number of
EFDs		 Resolution (Å) Mutant? Het group Links
2VF6 Human Fdps Synthase In Complex With Minodronate Farnesyl Pyrophosphate Synthetase 24 2.1 (1-Hydroxy-2-Imidazo[1,2-A]Pyridin-3-Ylethane-1,1-Diyl)Bis(Phosphonic Acid) • Magnesium Ion CSA • PDB • PDBSum
2RAH Human Fdps Synthase In Complex With Novel Inhibitor Farnesyl Pyrophosphate Synthetase 24 2.0 Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4DEM Crystal Structure Of Human Fpps In Complex With Ys_04_70 Farnesyl Pyrophosphate Synthase 24 1.85 [({4-[4-(Propan-2-Yloxy)Phenyl]Pyridin-2-Yl}Amino) Methanediyl]Bis(Phosphonic Acid) • Magnesium Ion CSA • PDB • PDBSum
2OPM Human Farnesyl Diphosphate Synthase Complexed With Bisphosphonate Bph-461 Farnesyl Pyrophosphate Synthetase (Fpp Synthetase) (Fps)(Farnesyl Diphosphate Synthetase) [Includes:Dimethylallyltranstransferase (Ec 2.5.1.1) • Geranyltranstransferase(Ec 2.5.1.10)] 24 2.4 Phosphate Ion
(2 more ⇓) 		CSA • PDB • PDBSum
1YV5 Human Farnesyl Diphosphate Synthase Complexed With Mg And Risedronate Farnesyl Pyrophosphate Synthetase 24 2.0 Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
2OPN Human Farnesyl Diphosphate Synthase Complexed With Bisphosphonate Bph-527 Farnesyl Pyrophosphate Synthetase (Fpp Synthetase) (Fps)(Farnesyl Diphosphate Synthetase) [Includes:Dimethylallyltranstransferase (Ec 2.5.1.1) • Geranyltranstransferase(Ec 2.5.1.10)] 24 2.7 Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
1YQ7 Human Farnesyl Diphosphate Synthase Complexed With Risedronate Farnesyl Pyrophosphate Synthetase 24 2.2 Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
3B7L Human Farnesyl Diphosphate Synthase Complexed With Mg And Minodronate Farnesyl Pyrophosphate Synthetase 24 1.95 Magnesium Ion • (1-Hydroxy-2-Imidazo[1,2-A]Pyridin-3-Ylethane-1,1-Diyl)Bis(Phosphonic Acid) CSA • PDB • PDBSum
3S4J Human Fdps Synthase In Complex With A Rigid Analog Of Risedronate Farnesyl Pyrophosphate Synthase 24 1.95 Yes 6,7-Dihydro-5H-Cyclopenta[B]Pyridine-6,6-Diylbis(Phosphonic Acid)
(2 more ⇓) 		CSA • PDB • PDBSum
3RYE Human Fdps Synthase In Complex With A N-Methyl Pyridinum Bisphosphonate Farnesyl Pyrophosphate Synthase 24 2.1 Yes 3-(2-Hydroxy-2,2-Diphosphonoethyl)-1-Methylpyridinium
(2 more ⇓) 		CSA • PDB • PDBSum
1ZW5 X-Ray Structure Of Farnesyl Diphosphate Synthase Protein Farnesyl Diphosphate Synthase 24 2.3 Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
3N46 Human Fpps Complex With Nov_980 And Zoledronic Acid/Mg2+ Farnesyl Pyrophosphate Synthase 24 2.35 (2R)-1-[(Benzyloxy)Carbonyl]-2,3-Dihydro-1H-Indole-2-Carboxylic Acid
(3 more ⇓) 		CSA • PDB • PDBSum
3N45 Human Fpps Complex With Fbs_04 And Zoledronic Acid/Mg2+ Farnesyl Pyrophosphate Synthase 24 1.88 (2S)-1-[(Benzyloxy)Carbonyl]-2,3-Dihydro-1H-Indole-2-Carboxylic Acid
(3 more ⇓) 		CSA • PDB • PDBSum
2F89 Crystal Structure Of Human Fpps In Complex With Pamidronate Farnesyl Diphosphate Synthase 24 2.6 Phosphate Ion
(2 more ⇓) 		CSA • PDB • PDBSum
2F8Z Crystal Structure Of Human Fpps In Complex With Zoledronate And Isopentenyl Diphosphate Farnesyl Diphosphate Synthase 24 2.6 Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
3N5H Human Fpps Complex With Nov_304 Farnesyl Pyrophosphate Synthase 24 2.2 3-(Carboxymethyl)-4,7-Dichloro-1H-Indole-2-Carboxylic Acid • Phosphate Ion CSA • PDB • PDBSum
3N3L Human Fpps Complex With Fbs_03 Farnesyl Pyrophosphate Synthase 24 2.74 (6-Methoxy-1-Benzofuran-3-Yl)Acetic Acid • Phosphate Ion CSA • PDB • PDBSum
2F94 Crystal Structure Of Human Fpps In Complex With Ibandronate Farnesyl Diphosphate Synthase 24 1.94 Zinc Ion
(2 more ⇓) 		CSA • PDB • PDBSum
2F92 Crystal Structure Of Human Fpps In Complex With Alendronate Farnesyl Diphosphate Synthase 24 2.15 Zinc Ion
(2 more ⇓) 		CSA • PDB • PDBSum
3N1V Human Fpps Complex With Fbs_01 Farnesyl Pyrophosphate Synthase 24 2.18 (5-Chloro-3-Methyl-1-Benzothiophen-2-Yl)Acetic Acid • Phosphate Ion CSA • PDB • PDBSum
3N1W Human Fpps Complex With Fbs_02 Farnesyl Pyrophosphate Synthase 24 2.56 (5-Chloro-1-Benzothiophen-3-Yl)Acetic Acid • Phosphate Ion CSA • PDB • PDBSum
2F9K Crystal Structure Of Human Fpps In Complex With Zoledronate And Zn2+ Farnesyl Diphosphate Synthase 24 2.06 Zinc Ion
(2 more ⇓) 		CSA • PDB • PDBSum
3N49 Human Fpps Complex With Nov_292 Farnesyl Pyrophosphate Synthase 24 2.5 Naphtho[2,1-B]Thiophen-1-Ylacetic Acid • Phosphate Ion CSA • PDB • PDBSum
3N6K Human Fpps Complex With Nov_823 Farnesyl Pyrophosphate Synthase 24 2.25 1-(Carboxymethyl)-1H-Benzo[G]Indole-2-Carboxylic Acid • Phosphate Ion CSA • PDB • PDBSum
2F7M Crystal Structure Of Unliganded Human Fpps Farnesyl Diphosphate Synthase 24 2.3 Phosphate Ion CSA • PDB • PDBSum
3N5J Human Fpps Complex With Nov_311 Farnesyl Pyrophosphate Synthase 24 2.35 3-(Carboxymethyl)-5,7-Dichloro-1H-Indole-2-Carboxylic Acid • Phosphate Ion CSA • PDB • PDBSum
2F8C Crystal Structure Of Fpps In Complex With Zoledronate Farnesyl Diphosphate Synthase 24 2.2 Phosphate Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4H5E Crystal Structure Of Human Fpps In Ternary Complex With Ys0470 And Isopentenyl Pyrophosphate Farnesyl Pyrophosphate Synthase 24 2.04 [({4-[4-(Propan-2-Yloxy)Phenyl]Pyridin-2-Yl}Amino) Methanediyl]Bis(Phosphonic Acid)
(2 more ⇓) 		CSA • PDB • PDBSum
4H5D Crystal Structure Of Human Fpps In Ternary Complex With Ys0470 And Inorganic Pyrophosphate Farnesyl Pyrophosphate Synthase 24 2.02 [({4-[4-(Propan-2-Yloxy)Phenyl]Pyridin-2-Yl}Amino) Methanediyl]Bis(Phosphonic Acid)
(2 more ⇓) 		CSA • PDB • PDBSum
4H5C Crystal Structure Of Human Fpps In Ternary Complex With Ys0470 And Inorganic Phosphate Farnesyl Pyrophosphate Synthase 24 2.02 [({4-[4-(Propan-2-Yloxy)Phenyl]Pyridin-2-Yl}Amino) Methanediyl]Bis(Phosphonic Acid)
(2 more ⇓) 		CSA • PDB • PDBSum
4GA3 Crystal Structure Of Human Farnesyl Diphosphate Synthase In Complex With Bph-1260 Farnesyl Pyrophosphate Synthase 24 2.39 1-Butyl-3-(2-Hydroxy-2,2-Diphosphonoethyl)-1H-Imidazol-3-Ium
(2 more ⇓) 		CSA • PDB • PDBSum
4LFV Crystal Structure Of Human Fpps In Complex With Ys0470 And Two Molecules Of Inorganic Phosphate Farnesyl Pyrophosphate Synthase 24 2.0 [({4-[4-(Propan-2-Yloxy)Phenyl]Pyridin-2-Yl}Amino) Methanediyl]Bis(Phosphonic Acid)
(3 more ⇓) 		CSA • PDB • PDBSum
4L2X Crystal Structure Of Human Fpps In Complex With Magnesium, Cl02134, And Inorganic Pyrophosphate Farnesyl Pyrophosphate Synthase 24 2.55 ({[6-(4-Cyclopropylphenyl)Thieno[2,3-D]Pyrimidin-4-Yl]Amino}Methanediyl)Bis(Phosphonic Acid)
(2 more ⇓) 		CSA • PDB • PDBSum
4JVJ Crystal Structure Of Human Fpps In Complex With Magnesium, Cl01131, And Sulfate Farnesyl Pyrophosphate Synthase 24 2.8 ({[6-(4-Methylphenyl)Thieno[2,3-D]Pyrimidin-4-Yl]Amino}Methanediyl)Bis(Phosphonic Acid)
(2 more ⇓) 		CSA • PDB • PDBSum
4LPH Crystal Structure Of Human Fpps In Complex With Cl03093 Farnesyl Pyrophosphate Synthase 24 2.3 Phosphate Ion • ({[6-(4-Methylphenyl)Thieno[2,3-D]Pyrimidin-4-Yl]Amino}Methyl)Phosphonic Acid CSA • PDB • PDBSum
4LPG Crystal Structure Of Human Fpps In Complex With Cl01131 Farnesyl Pyrophosphate Synthase 24 2.35 Phosphate Ion • ({[6-(4-Methylphenyl)Thieno[2,3-D]Pyrimidin-4-Yl]Amino}Methanediyl)Bis(Phosphonic Acid) CSA • PDB • PDBSum
4P0X Human Farnesyl Diphosphate Synthase In Complex With Taxodione Farnesyl Pyrophosphate Synthase 24 2.5 (5Beta)-11-Hydroxyabieta-7,9(11),13-Triene-6,12-Dione CSA • PDB • PDBSum
4P0W Human Farnesyl Diphosphate Synthase In Complex With Arenarone And Zoledronate Farnesyl Pyrophosphate Synthase 24 2.41 2-{[(1S,2R,4As,8Ar)-1,2,4A-Trimethyl-5-Methylidenedecahydronaphthalen-1-Yl]Methyl}Cyclohexa-2,5-Diene-1,4-Dione
(2 more ⇓) 		CSA • PDB • PDBSum
4PVY Crystal Structure Of Human Fpps In Complex With [({5-[4-(Propan-2-Yloxy)Phenyl]Pyridin-3-Yl}Amino)Methanediyl]Bis(Phosphonic Acid) Farnesyl Pyrophosphate Synthase 24 2.05 Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4PVX Crystal Structure Of Human Fpps In Complex With [({4-[4-(Cyclopropyloxy)Phenyl]Pyridin-2-Yl}Amino)Methanediyl]Bis(Phosphonic Acid) Farnesyl Pyrophosphate Synthase 24 2.18 Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4QXS Crystal Structure Of Human Fpps In Complex With Wc01088 Farnesyl Pyrophosphate Synthase 24 1.9 Phosphate Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4RXA Crystal Structure Of Human Farnesyl Diphosphate Synthase In Complex With Bph-1358 Farnesyl Pyrophosphate Synthase 24 2.2 N,N'-Bis[3-(4,5-Dihydro-1H-Imidazol-2-Yl) Phenyl]Biphenyl-4,4'-Dicarboxamide • Phosphate Ion CSA • PDB • PDBSum
4N1Z Crystal Structure Of Human Farnesyl Diphosphate Synthase In Complex With Bph-1222 Farnesyl Pyrophosphate Synthase 24 2.35 Phosphate Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4QPF New Lower Bone Affinity Bisphosphonate Drug Design For Effective Use In Diseases Characterized By Abnormal Bone Resorption Farnesyl Pyrophosphate Synthase 24 1.59 [1-Fluoro-2-(Imidazo[1,2-A]Pyridin-3-Yl)Ethane-1,1-Diyl]Bis(Phosphonic Acid) • Magnesium Ion CSA • PDB • PDBSum
2QIS Crystal Structure Of Human Farnesyl Pyrophosphate Synthase T210S Mutant Bound To Risedronate Farnesyl Pyrophosphate Synthetase 24 1.8 Yes Magnesium Ion • 1-Hydroxy-2-(3-Pyridinyl)Ethylidene Bis-Phosphonic Acid CSA • PDB • PDBSum
3CP6 Crystal Structure Of Human Farnesyl Diphosphate Synthase (T201A Mutant) Complexed With Mg And Biphosphonate Inhibitor Farnesyl Pyrophosphate Synthetase 24 1.95 Yes Magnesium Ion • (4As,7Ar)-Octahydro-1H-Cyclopenta[B]Pyridine-6,6-Diylbis(Phosphonic Acid) CSA • PDB • PDBSum
4KPD Crystal Structure Of Human Farnesyl Pyrophosphate Synthase (Y204F) Mutant Complexed With Mg, Risedronate And Isopentenyl Pyrophosphate Farnesyl Pyrophosphate Synthase 23 1.96 Yes Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4KFA Crystal Structure Of Human Farnesyl Pyrophosphate Synthase (T201A Mutant) Complexed With Mg And Zoledronate Farnesyl Pyrophosphate Synthase 24 1.98 Yes Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4KQU Crystal Structure Of Farnesyl Synthase Mutant (Y204A) Complexed With Mg, Alendronate And Isopentenyl Pyrophosphate Farnesyl Pyrophosphate Synthase 23 2.07 Yes Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4KQS Crystal Structure Of Farnesyl Pyrophosphate Synthase Mutant (Y204A) Complexed With Mg, Risedronate And Isopentenyl Pyrophosphate Farnesyl Pyrophosphate Synthase 23 1.97 Yes Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4KQ5 Crystal Structure Of Human Farnesyl Pyrophosphate Synthase Mutant (Y204A) Complexed With Mg And Zoledronate Farnesyl Pyrophosphate Synthase 23 2.4 Yes Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4KPJ Crystal Structure Of Farnesyl Pyrophosphate Synthase (Y204A) Mutant Complexed With Mg, Pamidronate Farnesyl Pyrophosphate Synthase 23 1.95 Yes Pamidronate
(2 more ⇓) 		CSA • PDB • PDBSum
4NG6 The Effects Of Lysine 200 And Phenylalanine 239 Farnesyl Pyrophosphate Synthase (Fpps) Mutations On The Catalytic Activity, Crystal Structure And Inhibition By Nitrogen Containing Bisphosphonates Farnesyl Pyrophosphate Synthase 23 2.35 Yes Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4Q23 The Role Of Threonine 201 And Tyrosine 204 In The Human Farnesyl Pyrophosphate Synthase Catalytic Mechanism And The Mode Of Inhibition By The Nitrogen-Containing Bisphosphonates Farnesyl Pyrophosphate Synthase 24 1.98 Yes 1-Hydroxy-2-(3-Pyridinyl)Ethylidene Bis-Phosphonic Acid
(2 more ⇓) 		CSA • PDB • PDBSum
4P0V Crystal Structure Of Human Farnesyl Diphosphoate Synthase In Complex With Zoledronate And Taxodione Farnesyl Pyrophosphate Synthase 24 2.4 Zoledronic Acid
(2 more ⇓) 		CSA • PDB • PDBSum
4N9U The Role Of Lysine 200 In The Human Farnesyl Pyrophosphate Synthase Catalytic Mechanism And The Mode Of Inhibition By The Nitrogen-Containing Bisphosphonates Farnesyl Pyrophosphate Synthase 23 2.11 Yes Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4NKF The Effects Of Lysine 200 And Phenylalanine 239 Farnesyl Pyrophosphate Synthase (Fpps) Mutations On The Catalytic Activity, Crystal Structure And Inhibition By Nitrogen Containing Bisphosphonates Farnesyl Pyrophosphate Synthase 23 2.0 Yes Magnesium Ion
(3 more ⇓) 		CSA • PDB • PDBSum
4NKE The Effects Of Lysine 200 And Phenylalanine 239 Farnesyl Pyrophosphate Synthase (Fpps) Mutations On The Catalytic Activity, Crystal Structure And Inhibition By Nitrogen Containing Bisphosphonates Farnesyl Pyrophosphate Synthase 23 1.46 Yes Magnesium Ion
(3 more ⇓) 		CSA • PDB • PDBSum
4OGU The Effects Of Lysine 200 And Phenylalanine 239 Farnesyl Pyrophosphate Synthase (Fpps) Mutations On The Catalytic Activity, Crystal Structure And Inhibition By Nitrogen Containing Bisphosphonates Farnesyl Pyrophosphate Synthase 23 2.1 Yes Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
4NUA The Effects Of Lysine 200 And Phenylalanine 239 Farnesyl Pyrophosphate Synthase (Fpps) Mutations On The Catalytic Activity, Crystal Structure And Inhibition By Nitrogen Containing Bisphosphonates Farnesyl Pyrophosphate Synthase 23 1.43 Yes 1-Hydroxy-2-(3-Pyridinyl)Ethylidene Bis-Phosphonic Acid
(3 more ⇓) 		CSA • PDB • PDBSum
Percent identity and alignment length from the BLAST match of the Functional Domain sequence to the PDB sequence.
"Yes" indicates that a GI associated with this Functional Domain was mapped to the PDB ID via UniProtKB.

Curation History
Time Change Annotation Old Value New Value
Nov. 4, 2014, 4:46 a.m. update curation agent holliday setDomainBoundaries.py
EC number assigned by UniProtKB accession ID.