2VFW

Rv1086 native

Summary for 2VFW

• Entry DOI: 10.2210/pdb2vfw/pdb
• Descriptor: SHORT-CHAIN Z-ISOPRENYL DIPHOSPHATE SYNTHETASE, SULFATE ION (3 entities in total)
• Functional Keywords: peptidoglycan synthesis, cell wall biogenesis/degradation, secreted, cell shape, transferase, prenyltransferase
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 2
• Total formula weight: 50706.77

Authors

Naismith, J.H.,Wang, W.,Dong, C. (deposition date: 2007-11-05, release date: 2007-11-13, Last modification date: 2024-05-08)

Primary citation

Wang, W.,Dong, C.,McNeil, M.,Kaur, D.,Mahapatra, S.,Crick, D.C.,Naismith, J.H.
The structural basis of chain length control in Rv1086.
J. Mol. Biol., 381:129-140, 2008

PubMed Abstract: 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.

PubMed: 18597781
DOI: 10.1016/j.jmb.2008.05.060

Experimental method

X-RAY DIFFRACTION (2.3 Å)