HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >

Structure analysis of geranyl pyrophosphate methyltransferase and the proposed reaction mechanism of SAM-dependent C-methylation

Files in This Item:
ACD68-11_1558-1569.pdf2.45 MBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/50689

Title: Structure analysis of geranyl pyrophosphate methyltransferase and the proposed reaction mechanism of SAM-dependent C-methylation
Authors: Ariyawutthiphan, Orapin Browse this author
Ose, Toyoyuki Browse this author →KAKEN DB
Minami, Atsushi Browse this author →KAKEN DB
Sinde, Sandip Browse this author
Tsuda, Muneya Browse this author
Gao, Yong-Gui Browse this author
Yao, Min Browse this author →KAKEN DB
Oikawa, Hideaki Browse this author →KAKEN DB
Tanaka, Isao Browse this author →KAKEN DB
Issue Date: Nov-2012
Publisher: International Union of Crystallography
Journal Title: Acta Crystallographica Section D: Biological Crystallography
Volume: 68
Issue: 11
Start Page: 1558
End Page: 1569
Publisher DOI: 10.1107/S0907444912038486
PMID: 23090405
Abstract: In the typical isoprenoid-biosynthesis pathway, condensation of the universal C5-unit precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) occurs via the common intermediates prenyl pyrophosphates (C10-C20). 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.
Type: article
URI: http://hdl.handle.net/2115/50689
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 尾瀬 農之

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


 

 - Hokkaido University