4f86
From Proteopedia
Structure analysis of Geranyl diphosphate methyltransferase in complex with GPP and sinefungin
Structural highlights
FunctionGPPMT_STRLS Catalyzes the SAM-dependent methylation of geranyl diphosphate (GPP) to yield (E)-2-methylgeranyl diphosphate (2-MeGPP). Publication Abstract from PubMedIn the typical isoprenoid-biosynthesis pathway, condensation of the universal C(5)-unit precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) occurs via the common intermediates prenyl pyrophosphates (C(10)-C(20)). The diversity of isoprenoids reflects differences in chain length, cyclization and further additional modification after cyclization. In contrast, the biosynthesis of 2-methylisonorneol (2-MIB), which is responsible for taste and odour problems in drinking water, is unique in that it primes the enzymatic methylation of geranyl pyrophosphate (GPP) before cyclization, which is catalyzed by an S-adenosyl-L-methionine-dependent methyltransferase (GPPMT). The substrate of GPPMT contains a nonconjugated olefin and the reaction mechanism is expected to be similar to that of the steroid methyltransferase (SMT) family. Here, structural analysis of GPPMT in complex with its cofactor and substrate revealed the mechanisms of substrate recognition and possible enzymatic reaction. Using the structures of these complexes, methyl-group transfer and the subsequent proton-abstraction mechanism are discussed. GPPMT and SMTs contain a conserved glutamate residue that is likely to play a role as a general base. Comparison with the reaction mechanism of the mycolic acid cyclopropane synthase (MACS) family also supports this result. This enzyme represented here is the first model of the enzymatic C-methylation of a nonconjugated olefin in the isoprenoid-biosynthesis pathway. In addition, an elaborate system to avoid methylation of incorrect substrates is proposed. Structure analysis of geranyl pyrophosphate methyltransferase and the proposed reaction mechanism of SAM-dependent C-methylation.,Ariyawutthiphan O, Ose T, Minami A, Sinde S, Tsuda M, Gao YG, Yao M, Oikawa H, Tanaka I Acta Crystallogr D Biol Crystallogr. 2012 Nov;68(Pt 11):1558-69. doi:, 10.1107/S0907444912038486. Epub 2012 Oct 18. PMID:23090405[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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