2vg1 | pdb_00002vg1
RV1086 E,E-FARNESYL DIPHOSPHATE COMPLEX
Structural highlights
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 PubMedIn 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
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