Farnesyl diphosphate synthase

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== Function ==
== Function ==
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'''Farnesyl diphosphate synthase''' (FPS) also named farnesyl pyrophosphate synthase catalyzes the conversion of geranyl diphosphate (GDP) and isopentenyl diphosphate (IPP) to farnesyl diphosphate and diphosphate<ref>PMID:11152452</ref>.
+
'''Farnesyl diphosphate synthase''' (FPS) also named farnesyl pyrophosphate synthase catalyzes the conversion of geranyl diphosphate (GDP) and isopentenyl diphosphate (IPP) to farnesyl diphosphate (FPP) and diphosphate (PP)<ref>PMID:11152452</ref>.
== Relevance ==
== Relevance ==
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**[[1fps]]– cFPS – chicken<br />
**[[1fps]]– cFPS – chicken<br />
**[[1ubv]] – cFPS (mutant) <br />
**[[1ubv]] – cFPS (mutant) <br />
-
**[[1zw5]], [[2f7m]] – hFPS – human<br />
+
**[[1zw5]], [[2f7m]], [[4xqr]], [[4xqs]], [[4xqt]] – hFPS – human<br />
**[[1rtr]]– FPS – ''Staphylococcus aureus''<br />
**[[1rtr]]– FPS – ''Staphylococcus aureus''<br />
**[[1yhk]] – TcFPS – ''Trypanosoma cruzi''<br />
**[[1yhk]] – TcFPS – ''Trypanosoma cruzi''<br />
**[[3lvs]], [[3m0g]] – FPS – ''Rhodobacter capsulatus''<br />
**[[3lvs]], [[3m0g]] – FPS – ''Rhodobacter capsulatus''<br />
**[[3m9u]] – LbFPS – ''Lactobacillus brevis''<br />
**[[3m9u]] – LbFPS – ''Lactobacillus brevis''<br />
 +
**[[5ayp]] – FPS – ''Geobacillus stearothermophilus''<br />
 +
**[[5hxn]] – z,z-FPS – tomato<br />
 +
**[[5hxo]] – z,z-FPS (mutant)<br />
*FPS binary complexes
*FPS binary complexes
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**[[1yq7]], [[1yv5]], [[2f89]], [[2f8c]], [[2f92]], [[2f94]], [[2f9k]], [[2rah]], [[2opn]], [[2vf6]], [[3b7l]], [[2opm]], [[3n1v]], [[3n1w]], [[3n3l]], [[3n45]], [[3n46]], [[3n49]], [[3n5j]], [[3n6k]], [[3n5h]], [[4dem]], [[4ga3]], [[4jvj]] - hFPS + inhibitor<br />
+
**[[1yq7]], [[1yv5]], [[2f89]], [[2f8c]], [[2f92]], [[2f94]], [[2f9k]], [[2rah]], [[2opn]], [[2vf6]], [[3b7l]], [[2opm]], [[3n1v]], [[3n1w]], [[3n3l]], [[3n45]], [[3n46]], [[3n49]], [[3n5j]], [[3n6k]], [[3n5h]], [[4dem]], [[4ga3]], [[4jvj]], [[4pvx]], [[4pvy]], [[4rxa]], [[5dgn]], [[5diq]], [[5djp]], [[5djr]], [[5djv]], [[5juz]], [[5jv0]], [[5jv1]], [[5jv2]], [[5ksx]] - hFPS + inhibitor<br />
**[[2qis]], [[3cp6]], [[3rye]], [[3s4j]], [[4n9u]] - hFPS (mutant) + inhibitor<br />
**[[2qis]], [[3cp6]], [[3rye]], [[3s4j]], [[4n9u]] - hFPS (mutant) + inhibitor<br />
**[[4kfa]], [[4kpj]], [[4kq5]] - hFPS (mutant) + osteoporosis drug<br />
**[[4kfa]], [[4kpj]], [[4kq5]] - hFPS (mutant) + osteoporosis drug<br />
**[[4lpg]], [[4lph]], [[4n1z]], [[4p0x]] - hFPS + drug<br />
**[[4lpg]], [[4lph]], [[4n1z]], [[4p0x]] - hFPS + drug<br />
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**[[4nfi]], [[4nfj]], [[4nfk]], [[4qxs]] - hFPS + bisphosphonate<br />
+
**[[4nfi]], [[4nfj]], [[4nfk]], [[4qxs]], [[4qpf]], [[5cg5]] - hFPS + bisphosphonate<br />
**[[4ng6]], [[4nke]], [[4nkf]], [[4nua]], [[4ogu]], [[4q23]] - hFPS (mutant) + bisphosphonate<br />
**[[4ng6]], [[4nke]], [[4nkf]], [[4nua]], [[4ogu]], [[4q23]] - hFPS (mutant) + bisphosphonate<br />
 +
**[[5dgm]], [[5dgs]] - hFPS + monophosphonate<br />
 +
**[[5ja0]] - hFPS + FPP<br />
**[[2i19]], [[2ewg]], [[2ogd]], [[2p1c]], [[3dyg]], [[3dyh]], [[3efq]], [[3egt]] - TbFPS + inhibitor – ''Trypanosoma brucei''<br />
**[[2i19]], [[2ewg]], [[2ogd]], [[2p1c]], [[3dyg]], [[3dyh]], [[3efq]], [[3egt]] - TbFPS + inhibitor – ''Trypanosoma brucei''<br />
**[[1ubw]], [[1ubx]] - cFPS (mutant) + GDP<br />
**[[1ubw]], [[1ubx]] - cFPS (mutant) + GDP<br />
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**[[1uby]] - cFPS (mutant) + dimethylallyl diphosphate<br />
+
**[[1uby]] - cFPS (mutant) + dimethylallyl PP<br />
**[[2for]]– FPS + IPP – ''Shigella flexneri''<br />
**[[2for]]– FPS + IPP – ''Shigella flexneri''<br />
**[[3id0]]– TcFPS + inhibitor<br />
**[[3id0]]– TcFPS + inhibitor<br />
**[[3pde]] – LbFPS + IPP<br />
**[[3pde]] – LbFPS + IPP<br />
 +
**[[5hxp]] – z,z-FPS (mutant) + IPP<br />
 +
**[[5hxq]] – z,z-FPS (mutant) + DMSPP<br />
*FPS ternary complexes
*FPS ternary complexes
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**[[4p0v]], [[4p0w]] - hFPS + 2 drugs<br />
**[[4p0v]], [[4p0w]] - hFPS + 2 drugs<br />
**[[4h5c]], [[4h3c]], [[4h5d]], [[4lfv]] - hFPS + phosphate + inhibitor<br />
**[[4h5c]], [[4h3c]], [[4h5d]], [[4lfv]] - hFPS + phosphate + inhibitor<br />
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**[[1rqi]] – EcFPS + IPP + dimethylallyl S-thiolodiphosphate – ''Escherichia coli''<br />
+
**[[5cg6]] - hFPS + IPP + bisphosphonate<br />
 +
**[[4l2x]] - hFPS + PP + inhibitor<br />
 +
**[[1rqi]] – EcFPS + IPP + dimethylallyl S-thioloPP – ''Escherichia coli''<br />
**[[1rqj]] - EcFPS + IPP + inhibitor<br />
**[[1rqj]] - EcFPS + IPP + inhibitor<br />
-
**[[1yhl]] – TcFPS + dimethylallyl diphosphate + inhibitor<br />
+
**[[1yhl]] – TcFPS + dimethylallyl PP + inhibitor<br />
**[[1yhm]], [[3iba]], [[3ick]], [[3icm]], [[3icn]], [[3icz]], [[4dwb]], [[4dwg]], [[4dxj]], [[4dzw]], [[4e1e]] - TcFPS + IPP + inhibitor<br />
**[[1yhm]], [[3iba]], [[3ick]], [[3icm]], [[3icn]], [[3icz]], [[4dwb]], [[4dwg]], [[4dxj]], [[4dzw]], [[4e1e]] - TcFPS + IPP + inhibitor<br />
**[[3ez3]] - PvFPS + IPP + inhibitor – ''Plasmodium vivax''<br />
**[[3ez3]] - PvFPS + IPP + inhibitor – ''Plasmodium vivax''<br />
**[[3dyf]] - TbFPS + IPP + inhibitor<br />
**[[3dyf]] - TbFPS + IPP + inhibitor<br />
 +
**[[5hxt]] – z,z-FPS (mutant) + DMSPP + IPP<br />
}}
}}
== References ==
== References ==

Revision as of 08:30, 14 May 2017

Human farnesyl diphosphate synthase complex with lipophylic bisphosphonate inhibitor and Mg+2 ions (green) (PDB code 2opm)

Drag the structure with the mouse to rotate

3D structures of farnesyl diphosphate synthase

Updated on 14-May-2017

References

  1. ↑ Schulbach MC, Mahapatra S, Macchia M, Barontini S, Papi C, Minutolo F, Bertini S, Brennan PJ, Crick DC. Purification, enzymatic characterization, and inhibition of the Z-farnesyl diphosphate synthase from Mycobacterium tuberculosis. J Biol Chem. 2001 Apr 13;276(15):11624-30. Epub 2001 Jan 4. PMID:11152452 doi:http://dx.doi.org/10.1074/jbc.M007168200
  2. ↑ Das S, Edwards PA, Crockett JC, Rogers MJ. Upregulation of endogenous farnesyl diphosphate synthase overcomes the inhibitory effect of bisphosphonate on protein prenylation in Hela cells. Biochim Biophys Acta. 2014 Apr 4;1841(4):569-73. doi:, 10.1016/j.bbalip.2013.12.010. Epub 2013 Dec 22. PMID:24369118 doi:http://dx.doi.org/10.1016/j.bbalip.2013.12.010
  3. ↑ Zhang Y, Cao R, Yin F, Hudock MP, Guo RT, Krysiak K, Mukherjee S, Gao YG, Robinson H, Song Y, No JH, Bergan K, Leon A, Cass L, Goddard A, Chang TK, Lin FY, Van Beek E, Papapoulos S, Wang AH, Kubo T, Ochi M, Mukkamala D, Oldfield E. Lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an X-ray and NMR investigation. J Am Chem Soc. 2009 Apr 15;131(14):5153-62. PMID:19309137 doi:10.1021/ja808285e
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