Undecaprenyl pyrophosphate synthase

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Function

Undecaprenyl pyrophosphate synthase or isoprenyl transferase or poly-cis-prenyltransferase or ditrans,polycis-undecaprenyl pyrophosphate synthase ((2E,6E) farnesyl diphosphate specific) (UPPS) catalyzes the consecutive condensation of farnesyl pyrophosphate (FPP) with 8 molecules of isopentenyl pyrophosphate (IPP) to produce undecaprenyl pyrophosphate. Undecaprenyl pyrophosphate serves as a lipid carrier for peptidoglycan synthesis of bacterial cell wall[1]. UPPS or NUS1 is a subunit of cis-prenyltransferase[2]. Bisphosphonate drugs are UPP inhibitors.

Relevance

UPPS inhibitors are investigated as potential antibacterials[3].

Structural highlights

The of UPPS (water molecules are shown as red spheres) contains an [4].

3D structures of undecaprenyl pyrophosphate synthase

Undecaprenyl pyrophosphate synthase 3D structures

References

  1. Guo RT, Ko TP, Chen AP, Kuo CJ, Wang AH, Liang PH. Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, isopentenyl pyrophosphate, and farnesyl thiopyrophosphate: roles of the metal ion and conserved residues in catalysis. J Biol Chem. 2005 May 27;280(21):20762-74. Epub 2005 Mar 23. PMID:15788389 doi:10.1074/jbc.M502121200
  2. Grabińska KA, Park EJ, Sessa WC. cis-Prenyltransferase: New Insights into Protein Glycosylation, Rubber Synthesis, and Human Diseases. J Biol Chem. 2016 Aug 26;291(35):18582-90. PMID:27402831 doi:10.1074/jbc.R116.739490
  3. Jukic M, Rozman K, Gobec S. Recent Advances in the Development of Undecaprenyl Pyrophosphate Synthase Inhibitors as Potential Antibacterials. Curr Med Chem. 2016;23(5):464-82. PMID:26718796
  4. Guo RT, Ko TP, Chen AP, Kuo CJ, Wang AH, Liang PH. Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, isopentenyl pyrophosphate, and farnesyl thiopyrophosphate: roles of the metal ion and conserved residues in catalysis. J Biol Chem. 2005 May 27;280(21):20762-74. Epub 2005 Mar 23. PMID:15788389 doi:10.1074/jbc.M502121200

Structure of E. coli UPP complex with isopentenyl pyrophosphate, phosphate and Mg+2 (green) (PDB code 1x07).

Drag the structure with the mouse to rotate

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Michal Harel, Alexander Berchansky