Biosynthesis of Isoprenoids: Characterization of a Functionally Active Recombinant 2-C-methyl-D-erythritol 4-phosphate Cytidyltransferase (IspD) from Mycobacterium tuberculosis H37Rv

Shi, Wenjing; Jiao, Feng; Zhang, Min; Lai, Xuhui; Xu, Shengfeng; Zhang, Xuelian; Wang, Honghai

doi:10.5483/bmbrep.2007.40.6.911

Cited by 18 publications

(19 citation statements)

References 31 publications

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“…Studies by Putra et al (1998) revealed that M. tuberculosis does not incorporate radiolabelled mevalonate, suggesting the MEP pathway as the primary source of IPP. This pathogen has been the focus of numerous studies in recent years, and several of the pathway genes have been characterized and shown to play an essential role during in vitro growth, including dxs (Bailey et al, 2002), dxr (ispC) (Brown & Parish, 2008), yghP (ispD) (Eoh et al, 2009;Shi et al, 2007), ychB (ispE) (Eoh et al, 2009) and yghB (ispF) (Buetow et al, 2007). An extensive study by Brown et al (2010) further demonstrated the essentiality of the dxs and gcpE (ispG) genes.…”

Section: Other Pathogensmentioning

confidence: 99%

“…The IspD/ YghP enzyme of M. tuberculosis was cloned and expressed in an E. coli system, and the purified recombinant protein was subjected to biochemical and enzymic characterization in order to gain insight into the structure of this protein for therapeutic drug design (Shi et al, 2007). A recent publication by Tsang et al (2011) details the kinetic characterization of the IspD enzyme of Francisella tularensis, and their results validate the targeting of this enzyme for novel therapeutics against F. tularensis.…”

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confidence: 99%

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Isoprenoid biosynthesis in bacterial pathogens

et al. 2012

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Section: Other Pathogensmentioning

confidence: 99%

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confidence: 99%

Isoprenoid biosynthesis in bacterial pathogens

et al. 2012

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“…The first motif is very similar to a previously reported motif, AAGXGXRX 5 . This phenomenon has also been reported for other IspD proteins (18) and therefore suggests that the catalytic mechanism of AbpA is similar to that of IspD.…”

Section: Figmentioning

confidence: 56%

Biochemical Characterization of the CDP- d -Arabinitol Biosynthetic Pathway in Streptococcus pneumoniae 17F

Wang

Perepelov

et al. 2012

J Bacteriol

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Streptococcus pneumoniae is a major human pathogen associated with many diseases worldwide. Capsular polysaccharides (CPSs) are the major virulence factor. The biosynthetic pathway of D-arabinitol, which is present in the CPSs of several S. pneumoniae serotypes, has never been identified. In this study, the genes abpA (previously known as abp1) and abpB (previously known as abp2), which have previously been reported to be responsible for nucleoside diphosphate (NDP)-D-arabinitol (the nucleotide-activated form of D-arabinitol) synthesis, were cloned. The enzyme products were overexpressed, purified, and analyzed for their respective activities. Novel products produced by AbpA-and AbpB-catalyzing reactions were detected by capillary electrophoresis, and the structures of the products were elucidated using electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. As a result, abpA was identified to be a

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“…Inhibitors were designed for the development of new antibiotics and herbicide18192021. On the other hand, the MEP pathway underlines the biosynthesis of valuable isoprenoids by bacteria cell, the enhancement of the MEP pathway resulted in higher yield of various products, including isoprene, lycopene2223, artemisinic acid24, taxadiene25, carotenoids26, et al .…”

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confidence: 99%

A structural and functional study on the 2-C-methyl-d-erythritol-4-phosphate cytidyltransferase (IspD) from Bacillus subtilis

Jin

Liu

et al. 2016

Sci Rep

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2-C-Methyl-D-erythritol-4-phosphate cytidyltransferase (IspD) is an essential enzyme in the mevalonate-independent pathway of isoprenoid biosynthesis. This enzyme catalyzes 2-C-Methyl-d-erythritol 4-phosphate (MEP) and cytosine triphosphate (CTP) to 4-diphosphocytidyl-2-C-methyl-d-erythritol (CDPME) and inorganic pyrophosphate (PPi). Bacillus subtilis was a kind of excellent isoprene producer. However, the studies on the key enzymes of MEP pathway in B. subtilis were still absent. In this work, the crystal structures of IspD and IspD complexed with CTP from B.subtilis were determined. For the first time, the intact P-loop was observed in the apo structure of IspD enzyme. Structural comparisons revealed that the concerted movements of the P-loop and loops close to the active site were essential in the reaction catalyzed by IspD. Meanwhile, kinetic analysis showed that the CTP hydrolytic activity of IspD from B.subtilis was over two times higher than that from Escherichia coli. These results will be useful for future target-based screening of potential inhibitors and the metabolic engineering for isoprenoid biosynthesis.

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Biosynthesis of Isoprenoids: Characterization of a Functionally Active Recombinant 2-C-methyl-D-erythritol 4-phosphate Cytidyltransferase (IspD) from Mycobacterium tuberculosis H37Rv

Cited by 18 publications

References 31 publications

Isoprenoid biosynthesis in bacterial pathogens

Isoprenoid biosynthesis in bacterial pathogens

Biochemical Characterization of the CDP- d -Arabinitol Biosynthetic Pathway in Streptococcus pneumoniae 17F

A structural and functional study on the 2-C-methyl-d-erythritol-4-phosphate cytidyltransferase (IspD) from Bacillus subtilis

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