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Gene Review:

ECs0175 - 1-deoxy-D-xylulose 5-phosphate...

Escherichia coli O157:H7 str. Sakai

Altincicek, B. et al., Henriksson, L.M. et al., Kuzuyama, T. et al., Steinbacher, S. et al., Grolle, S. et al., et al.

Steinbacher, Kaiser, Eisenreich, Huber, Bacher, Rohdich,

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Disease relevance of ECs0175

These results indicate that Glu(231) of E. coli DXP reductoisomerase plays an important role(s) in the conversion of DXP to 2-C-methyl-d-erythritol 4-phosphate, and that His(153), His(209), and His(257), in part, associate with DXP binding in the enzyme molecule [1].
The 1.9 A resolution structure of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a potential drug target [2].
Tools for discovery of inhibitors of the 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase: an approach with enzymes from the pathogenic bacterium Pseudomonas aeruginosa [3].
Deoxyxylulose 5-phosphate (DXP) analogs were synthesized and evaluated as alternative substrates and inhibitors of recombinant Synechocystis PCC6803 DXP reductoisomerase (DXR; EC 1.1.1.267) [4].

High impact information on ECs0175

Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC). Implications for the catalytic mechanism and anti-malaria drug development [5].
2-C-Methyl-d-erythritol 4-phosphate synthase (IspC) is the first enzyme committed to isoprenoid biosynthesis in the methylerythritol phosphate pathway, which represents an alternative route to the classical mevalonate pathway [5].
Diethyl pyrocarbonate treatment inactivated DXP reductoisomerase, and subsequent hydroxylamine treatment restored the activity of the diethyl pyrocarbonate-treated enzyme [1].
2-C-Methyl-D-erythritol-4-phosphate synthase (MEP synthase) catalyzes the rearrangement/reduction of 1-D-deoxyxylulose-5-phosphate (DXP) to methylerythritol-4-phosphate (MEP) as the first pathway-specific reaction in the MEP biosynthetic pathway to isoprenoids [6].
Biochemical characterization of the purified DXP reductoisomerase showed a strict dependence of the enzyme on NADPH and divalent cations (Mn(2+), Co(2+) or Mg(2+)) [7].

Chemical compound and disease context of ECs0175

However, spontaneous mutations in Escherichia coli were observed to rescue the otherwise lethal loss of the first two enzymes of the pathway, 1-deoxy-D-xylulose 5-phosphate (DXP) synthase (DXS) and DXP reductoisomerase (DXR), with a relatively high frequency [8].
Two Pseudomonas aeruginosa genes encoding the enzymes 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase, both involved in the mevalonate-independent biosynthesis of isoprenoids, have been expressed as recombinant enzymes in Escherichia coli [3].

Biological context of ECs0175

The deduced amino acid sequence showed the highest identity (48.2%) to the DXP reductoisomerase of Escherichia coli [7].

Associations of ECs0175 with chemical compounds

1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzes the NADPH-dependent rearrangement and reduction of 1-deoxy-D-xylulose 5-phosphate to form 2-C-methyl-D-erythritol 4-phosphate, as the second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway found in many bacteria and plants [2].
The purified P. aeruginosa DXP reductoisomerase was inhibited by submicromolar concentrations of the antibiotics fosmidomycin and FR-900098 in a well established method [3].

References

Characterization of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, an enzyme involved in isopentenyl diphosphate biosynthesis, and identification of its catalytic amino acid residues. Kuzuyama, T., Takahashi, S., Takagi, M., Seto, H. J. Biol. Chem. (2000) [Pubmed]
The 1.9 A resolution structure of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a potential drug target. Henriksson, L.M., Björkelid, C., Mowbray, S.L., Unge, T. Acta Crystallogr. D Biol. Crystallogr. (2006) [Pubmed]
Tools for discovery of inhibitors of the 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase: an approach with enzymes from the pathogenic bacterium Pseudomonas aeruginosa. Altincicek, B., Hintz, M., Sanderbrand, S., Wiesner, J., Beck, E., Jomaa, H. FEMS Microbiol. Lett. (2000) [Pubmed]
Substrate analogs for the investigation of deoxyxylulose 5-phosphate reductoisomerase inhibition: synthesis and evaluation. Phaosiri, C., Proteau, P.J. Bioorg. Med. Chem. Lett. (2004) [Pubmed]
Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC). Implications for the catalytic mechanism and anti-malaria drug development. Steinbacher, S., Kaiser, J., Eisenreich, W., Huber, R., Bacher, A., Rohdich, F. J. Biol. Chem. (2003) [Pubmed]
E. coli MEP synthase: steady-state kinetic analysis and substrate binding. Koppisch, A.T., Fox, D.T., Blagg, B.S., Poulter, C.D. Biochemistry (2002) [Pubmed]
Isolation of the dxr gene of Zymomonas mobilis and characterization of the 1-deoxy-D-xylulose 5-phosphate reductoisomerase. Grolle, S., Bringer-Meyer, S., Sahm, H. FEMS Microbiol. Lett. (2000) [Pubmed]
A mutant pyruvate dehydrogenase E1 subunit allows survival of Escherichia coli strains defective in 1-deoxy-D-xylulose 5-phosphate synthase. Sauret-Güeto, S., Urós, E.M., Ibáñez, E., Boronat, A., Rodríguez-Concepción, M. FEBS Lett. (2006) [Pubmed]

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