Farnesyl diphosphate synthase
From Proteopedia
(Difference between revisions)
| Line 12: | Line 12: | ||
== Structure == | == Structure == | ||
| - | FPPS exists as a homodimer, with each monomer having an active site. The monomers have the characteristic FPPS fold of a ten-helix bundle and four other helices that run perpendicular to the bundle. There are two substrate sites, one is allylic and the other is homoallylic. GPP and DMAPP bind to the allylic site, while IPP binds to the homoallylic site. These two sites are connected to the top of the bundle and exist as part of a cavity. [1] Another characteristic feature of all FPPS enzymes are two highly conserved aspartate rich motifs. These motifs are called First Aspartate Rich Motif (FARM) and Second Aspartate Rich Motif (SARM), and have sequences of DDXX(XX)D and DDXXD respectively. FARM and SARM are found on opposite sides on the active site cavity facing one another. [2] | + | FPPS exists as a homodimer, with each monomer having an active site. The monomers have the characteristic FPPS fold of a ten-helix bundle and four other helices that run perpendicular to the bundle. There are two substrate sites, one is allylic and the other is homoallylic. GPP and DMAPP bind to the allylic site, while IPP binds to the homoallylic site. These two sites are connected to the top of the bundle and exist as part of a cavity. [1] Another characteristic feature of all FPPS enzymes are two highly conserved aspartate rich motifs. These motifs are called <scene name='48/485622/Lmfpps_rbs/3'>First Aspartate Rich Motif (FARM) and Second Aspartate Rich Motif (SARM)</scene>, and have sequences of DDXX(XX)D and DDXXD respectively. FARM and SARM are found on opposite sides on the active site cavity facing one another. [2] |
When FPPS interacts with bisphosphonates, the bisphosphonates bind in the homoallylic binding sites and are coordinated by three divalent cations (Ca 2+ or Mg 2+). | When FPPS interacts with bisphosphonates, the bisphosphonates bind in the homoallylic binding sites and are coordinated by three divalent cations (Ca 2+ or Mg 2+). | ||
Revision as of 17:31, 15 July 2020
| |||||||||||
|
References
- ↑ 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
- ↑ 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
- ↑ Selby P. Alendronate treatment for osteoporosis: a review of the clinical evidence. Osteoporos Int. 1996;6(6):419-26. doi: 10.1007/bf01629572. PMID:9116385 doi:http://dx.doi.org/10.1007/bf01629572
- ↑ 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
Proteopedia Page Contributors and Editors (what is this?)
Hannah Campbell, Michal Harel, Tihitina Y Aytenfisu, Alexander Berchansky, Joel L. Sussman, Sandra B. Gabelli
