| Structural highlights
2vg1 is a 2 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | 2vfw, 2vg0 |
| Activity: | (2Z,6E)-farnesyl diphosphate synthase, with EC number 2.5.1.68 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ZFPP_MYCTU] Catalyzes the condensation of only one isopentenyl pyrophosphate (IPP) unit in the cis configuration to E-geranyl diphosphate (E-GPP) generating the 15 carbon product (2Z,6E)-farnesyl diphosphate (Z-FPP or EZ-FPP). Z-FPP is the precursor of decaprenyl diphosphate, which has a central role in the biosynthesis of the mycobacterial cell wall.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
In Mycobacterium tuberculosis, two related Z-prenyl diphosphate synthases, E,Z-farnesyl diphosphate synthase (Rv1086) and decaprenyl diphosphate synthase (Rv2361c), work in series to synthesize decaprenyl phosphate (C(50)) from isopentenyl diphosphate and E-geranyl diphosphate. Decaprenyl phosphate plays a central role in the biosynthesis of essential mycobacterial cell wall components, such as the mycolyl-arabinogalactan-peptidoglycan complex and lipoarabinomannan; thus, its synthesis has attracted considerable interest as a potential therapeutic target. Rv1086 is a unique prenyl diphosphate synthase in that it adds only one isoprene unit to geranyl diphosphate, generating the 15-carbon product (E,Z-farnesyl diphosphate). Rv2361c then adds a further seven isoprene units to E,Z-farnesyl diphosphate in a processive manner to generate the 50-carbon prenyl diphosphate, which is then dephosphorylated to generate a carrier for activated sugars. The molecular basis for chain-length discrimination by Rv1086 during synthesis is unknown. We also report the structure of apo Rv1086 with citronellyl diphosphate bound and with the product mimic E,E-farnesyl diphosphate bound. We report the structures of Rv2361c in the apo form, with isopentenyl diphosphate bound and with a substrate analogue, citronellyl diphosphate. The structures confirm the enzymes are very closely related. Detailed comparison reveals structural differences that account for chain-length control in Rv1086. We have tested this hypothesis and have identified a double mutant of Rv1086 that makes a range of longer lipid chains.
The structural basis of chain length control in Rv1086.,Wang W, Dong C, McNeil M, Kaur D, Mahapatra S, Crick DC, Naismith JH J Mol Biol. 2008 Aug 1;381(1):129-40. Epub 2008 Jul 1. PMID:18597781[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Crick DC, Schulbach MC, Zink EE, Macchia M, Barontini S, Besra GS, Brennan PJ. Polyprenyl phosphate biosynthesis in Mycobacterium tuberculosis and Mycobacterium smegmatis. J Bacteriol. 2000 Oct;182(20):5771-8. PMID:11004176
- ↑ Schulbach MC, Brennan PJ, Crick DC. Identification of a short (C15) chain Z-isoprenyl diphosphate synthase and a homologous long (C50) chain isoprenyl diphosphate synthase in Mycobacterium tuberculosis. J Biol Chem. 2000 Jul 28;275(30):22876-81. PMID:10816587 doi:http://dx.doi.org/10.1074/jbc.M003194200
- ↑ 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
- ↑ Wang W, Dong C, McNeil M, Kaur D, Mahapatra S, Crick DC, Naismith JH. The structural basis of chain length control in Rv1086. J Mol Biol. 2008 Aug 1;381(1):129-40. Epub 2008 Jul 1. PMID:18597781 doi:10.1016/j.jmb.2008.05.060
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