Undecaprenyl pyrophosphate synthase

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