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| - | <StructureSection load='1x07' size='340' side='right' caption='Structure of E. coli UPP complex with isopentenyl pyrophosphate, phosphate and Mg+2 (green) (PDB code [[1x07]]).' scene=''> | + | <StructureSection load='1x07' size='350' side='right' caption='Structure of E. coli UPP complex with isopentenyl pyrophosphate, phosphate and Mg+2 (green) (PDB code [[1x07]]).' scene='59/591995/Cv/4' pspeed='8'> |
| | | | |
| | == Function == | | == 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<ref>PMID:15788389</ref>. '''UPPS''' or '''NUS1''' is a subunit of ''cis''-prenyltransferase<ref>PMID:27402831</ref>. Bisphosphonate drugs are UPP inhibitors. |
| - | '''Undecaprenyl pyrophosphate synthase''' (UPP) 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. Bisphosphonate drugs are UPP inhibitors. | + | |
| - | | + | |
| - | == Disease ==
| + | |
| | | | |
| | == Relevance == | | == Relevance == |
| | + | UPPS inhibitors are investigated as potential antibacterials<ref>PMID:26718796</ref>. |
| | | | |
| | == Structural highlights == | | == Structural highlights == |
| | + | The <scene name='59/591995/Cv/5'>active site</scene> of UPPS (water molecules are shown as red spheres) contains an <scene name='59/591995/Cv/6'>octahedrally coordinated Mg+2 ion bound to the pyrophosphate group of isopentenyl pyrophosphate</scene><ref>PMID:15788389</ref>. |
| | | | |
| | ==3D structures of undecaprenyl pyrophosphate synthase== | | ==3D structures of undecaprenyl pyrophosphate synthase== |
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| - | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
| + | [[Undecaprenyl pyrophosphate synthase 3D structures]] |
| - | | + | |
| - | [[1f75]] – UPP (mutant) – ''Micrococcus luteus''<br /> | + | |
| - | [[3qas]] – EcUPP – ''Escherichia coli''<br />
| + | |
| - | [[1jp3]] – EcUPP (mutant) <br />
| + | |
| - | [[2d2r]] – HpUPP (mutant) – ''Helicobacter pylori''<br />
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| - | | + | |
| - | ===UPP complexes===
| + | |
| - | | + | |
| - | [[1ueh]] – EcUPP + Mg + SO4 + triton<br />
| + | |
| - | [[1v7u]] – EcUPP + FPP <br />
| + | |
| - | [[1x06]] – EcUPP + Mg + FPP analog + IPP<br />
| + | |
| - | [[1x08]] – EcUPP (mutant) + Mg + FPP analog + IPP<br />
| + | |
| - | [[1x07]] – EcUPP + Mg + PO4 + IPP<br />
| + | |
| - | [[1x09]] – EcUPP (mutant) + Mg + IPP<br />
| + | |
| - | [[2e98]], [[2e99]], [[2e9a]], [[2e9c]], [[2e9d]], [[3th8]], [[3sgt]], [[3sgv]], [[3sgx]], [[3sh0]], [[4h2j]], [[4h2m]], [[4h2o]], [[4h38]], [[4h3c]], [[4h3a]], [[4h8e]] – EcUPP + bisphosphonate<br />
| + | |
| - | [[2dtn]] – HpUPP + pyrophosphate<br />
| + | |
| - | [[3ugs]] - UPP + FPP analog – ''Campylobacter jejuni''<br />
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| - | | + | |
| | | | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| - | | + | </StructureSection> |
| | [[Category:Topic Page]] | | [[Category:Topic Page]] |
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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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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