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1-Deoxy-D-Xylulose 5-Phosphate (DXP) Synthase is an enzyme that catalyzes the formation of DXP via the condensation of D-glyceraldehyde 3-phosphate (D-GAP) and pyruvate in a thiamine diphosphate dependent manner. Along with D-GAP as the acceptor substrate, it also catalyzes the decarboxylation of pyruvate and the condensation of hydroxyethyl-ThDP intermediates. DXP synthase is a potential target for anti-infective drug developments because of its role in pathogen metabolism and in isoprenoid biosynthesis. It operates via a ping-pong mechanism in a manner similar to other ThDP-dependent enzymes; however, DXP synthase is unique because of its structural features which differs the way it binds substrates. It utilizes random sequential mechanisms that require the formation of a ternary complex among pyruvate derived LThDP and D-GAP. This distinction makes it possible to develop selective inhibitors of the enzyme that will help towards the development of anti-infective agents that target early stage isoprenoid biosynthesis.

Function
DXP synthase is found in bacteria and in plants. Samples of DXP synthase for the studies of the development of anti-infective agents were taken from bacteria; Escherichia coli and Haemophilus influenzae to be exact. In plants, DXP synthase acts as a regulatory enzyme in the mevalonate-independent pathway (MEP pathway) for terpenoid biosynthesis. Terpenoids are a large class of organic chemicals derived from plants that have some important pharmacological activity.

Specifically, in the Methylerythritol Phosphate (MEP) Pathway for isoprenoid biosynthesis, DXP synthase is used in the first step in order to produce DXP. DXP so far is the only one that stabilizes the predecarboxylation intermediate, C2-alpha-lactyl-thiamin-diphosphate (LThDP) within the thiamin diphosphate (ThDP)-dependent enzymes.

When stored as undiluted stock at -20°C, DXP Synthase will be stable for at least 6 months.

History
DXP synthase was primarily discovered in 1997 in an attempt to create anti-infective drugs specifically targetting the biosynthesis of Isoprenoids found in most pathogens. The enzyme was revealed to be the first step in the Methylerythritol Phosphate (MEP) Pathway used to synthesize the bioprecursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) of isoprenoids.

Mechanism
DXP synthase catalyzes the covalent C-C between D-GAP and pyruvate.

http://www.jbc.org/content/286/42/36522.full.pdf

https://www.ebi.ac.uk/interpro/entry/IPR005477

https://pubs.acs.org/doi/10.1021/acs.biochem.8b00548

http://www.echelon-inc.com/index.php?module=Products&func=detail&id=941

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946878/pdf/nihms528953.pdf

http://www.pnas.org/content/pnas/114/35/9355.full.pdf

http://www.brenda-enzymes.org/all_enzymes.php?ecno=2.2.1.7&table=Molecular_Weight

http://grantome.com/grant/NIH/F31-AI094967-01

http://www.jbc.org/content/286/42/36522