Target type: molecularfunction
Catalysis of the reaction: 2-C-methyl-D-erythritol 4-phosphate + NADP+ = 1-deoxy-D-xylulose 5-phosphate + H+ + NADPH. [EC:1.1.1.267, RHEA:13717]
1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is a crucial enzyme involved in the biosynthesis of isoprenoids, a diverse class of essential biomolecules. It catalyzes the reversible conversion of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP), a key step in the non-mevalonate pathway. This pathway, found in bacteria, plants, and some protozoa, provides the essential building blocks for the synthesis of isoprenoids, which encompass a wide range of molecules with diverse functions:
* **Terpenes:** A large group of hydrocarbons and their oxygenated derivatives, contributing to fragrances, pigments, and plant defense compounds.
* **Steroids:** Crucial for cell signaling, hormone synthesis, and membrane structure.
* **Carotenoids:** Pigments essential for photosynthesis and protection from oxidative stress.
* **Ubiquinone:** A vital electron carrier in cellular respiration.
* **Dolichol:** Involved in protein glycosylation, a critical process in protein modification and function.
The DXR enzyme utilizes a complex mechanism to catalyze the isomerization and reduction of DXP to MEP. This mechanism involves:
1. **Isomerization:** DXR rearranges the carbon skeleton of DXP, converting the keto group to an enol form.
2. **NADPH-dependent reduction:** DXR utilizes NADPH as a reducing agent to convert the enol to a hydroxyl group, forming MEP.
The DXR enzyme is a crucial target for the development of antimicrobial agents. Many pathogenic bacteria, including Mycobacterium tuberculosis, rely heavily on the non-mevalonate pathway for their survival. Targeting DXR specifically inhibits the synthesis of essential isoprenoids, effectively disrupting bacterial growth and replication.
DXR inhibitors are actively being researched and developed as promising candidates for the treatment of bacterial infections.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| 1-deoxy-D-xylulose 5-phosphate reductoisomerase | A 1-deoxy-D-xylulose 5-phosphate reductoisomerase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P45568] | Escherichia coli K-12 |
| 1-deoxy-D-xylulose 5-phosphate reductoisomerase, chloroplastic | A 1-deoxy-D-xylulose 5-phosphate reductoisomerase that is encoded in the genome of Arabidopsis thaliana. [OMA:Q9XFS9, PRO:DNx] | Arabidopsis thaliana (thale cress) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| fosmidomycin | fosmidomycin : Propylphosphonic acid in which one of the hydrogens at position 3 is substituted by a formyl(hydroxy)amino group. An antibiotic obtained from Streptomyces lavendulae, it specifically inhibits DXP reductoisomerase (EC 1.1.1.267), a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. fosmidomycin: from Streptomyces lavendulae; RN given refers to parent cpd; structure in second source | hydroxamic acid; phosphonic acids | antimicrobial agent; bacterial metabolite; EC 1.1.1.267 (1-deoxy-D-xylulose-5-phosphate reductoisomerase) inhibitor |
| 3-aminopropylphosphonic acid | (3-aminopropyl)phosphonic acid : A phosphonic acid in which the hydrogen attached to the phosphorus of phosphonic acid is substituted by a 3-aminopropyl group. It is a partial agonist of GABAB receptors. 3-aminopropylphosphonic acid: RN given refers to parent cpd; structure | phosphonic acids; primary amino compound; zwitterion | GABAB receptor agonist |
| n-hydroxy-4-phosphonobutanamide | N-hydroxy-4-phosphonobutanamide: structure given in first source | ||
| 3-(n-acetyl-n-hydroxy)aminopropylphosphonic acid | 3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid: from Streptomyces rubellomurinus sp. nov.; interferes with bacterial cell wall synthesis; structure in first source | phosphonoacetic acid | |
| fosmidomycin monosodium salt | |||
| quercetin | 7-hydroxyflavonol; pentahydroxyflavone | antibacterial agent; antineoplastic agent; antioxidant; Aurora kinase inhibitor; chelator; EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor; geroprotector; phytoestrogen; plant metabolite; protein kinase inhibitor; radical scavenger | |
| luteolin | 3'-hydroxyflavonoid; tetrahydroxyflavone | angiogenesis inhibitor; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; c-Jun N-terminal kinase inhibitor; EC 2.3.1.85 (fatty acid synthase) inhibitor; immunomodulator; nephroprotective agent; plant metabolite; radical scavenger; vascular endothelial growth factor receptor antagonist | |
| baicalein | trihydroxyflavone | angiogenesis inhibitor; anti-inflammatory agent; antibacterial agent; anticoronaviral agent; antifungal agent; antineoplastic agent; antioxidant; apoptosis inducer; EC 1.13.11.31 (arachidonate 12-lipoxygenase) inhibitor; EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor; EC 4.1.1.17 (ornithine decarboxylase) inhibitor; ferroptosis inhibitor; geroprotector; hormone antagonist; plant metabolite; prostaglandin antagonist; radical scavenger | |
| fisetin | 3'-hydroxyflavonoid; 7-hydroxyflavonol; tetrahydroxyflavone | anti-inflammatory agent; antioxidant; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; geroprotector; metabolite; plant metabolite | |
| myricetin | 7-hydroxyflavonol; hexahydroxyflavone | antineoplastic agent; antioxidant; cyclooxygenase 1 inhibitor; food component; geroprotector; hypoglycemic agent; plant metabolite |