Disease relevance of C01216

• Altered transport properties in Escherichia coli mutants selected for pH-conditional growth on 3-deoxy-2-oxo-D-gluconate [1].
• Structure of Thermus thermophilus 2-Keto-3-deoxygluconate kinase: evidence for recognition of an open chain substrate [2].
• 2-keto-3-deoxygluconate transport system in Erwinia chrysanthemi [3].
• D-Galactose was the initial substrate of the De Ley-Doudoroff pathway, involving reactions of NAD-dependent oxidation of D-galactose to D-galactonate, its dehydration to 2-keto-3-deoxy-D-galactonate, and its phosphorylation to 2-keto-3-deoxy-D-galactonate 6-phosphate [4].

High impact information on C01216

• Metabolic pathway promiscuity in the archaeon Sulfolobus solfataricus revealed by studies on glucose dehydrogenase and 2-keto-3-deoxygluconate aldolase [5].
• All these genes, including kdgT which encodes the 2-keto-3-deoxygluconate (KDG) transport system, are negatively regulated by the KdgR protein [6].
• Known examples include NAL, dihydrodipicolinate synthetase (DHDPS), d-5-keto-4-deoxyglucarate dehydratase, 2-keto-3-deoxygluconate aldolase, trans-o-hydroxybenzylidenepyruvate hydrolase-aldolase and trans-2'-carboxybenzalpyruvate hydratase-aldolase [7].
• Sulfolobus solfataricus is a hyperthermophilic archaeon growing optimally at 80-85 degrees C. It metabolizes glucose via a novel non-phosphorylated Entner-Doudoroff pathway, in which the reversible C(6) to C(3) aldol cleavage is catalysed by 2-keto-3-deoxygluconate aldolase (KDG-aldolase), generating pyruvate and glyceraldehyde [8].
• Genetic and kinetic evidence is presented to show that the carrier-mediated uptake of the anionic sugars 3-deoxy-2-oxo-D-gluconate and D-glucuronate by Escherichia coli involves the concomitant transport of protons [9].

Biological context of C01216

• The 2-keto-3-deoxygluconate entry reaction displayed saturation kinetics, with an apparent Km of 0.52 mM (at 30 degrees C and pH 7) [3].
• Construction and expression of hybrid plasmids containing the structural gene of the Escherichia coli K-12 3-deoxy-2-oxo-D-gluconate transport system [10].
• We introduced a kdgT-lac fusion into the E. chrysanthemi chromosome by marker exchange recombination and studied its regulation. kdgT product synthesis was not induced by external 2-keto-3-deoxygluconate in the wild-type strain but was induced by galacturonate and polygalacturonate [3].
• The operon consists of four genes: kdgR, encoding the putative regulator protein; kdgK, encoding 2-keto-3-deoxygluconate kinase; kdgA, encoding 2-keto-3-deoxygluconate-6-phosphate aldolase; and kdgT, encoding a transporter [11].
• But, the genome database shows that this microorganism has a gene (kdgK) encoding 2-keto-3-deoxy-D-gluconate (KDG) kinase (KDGK) which phosphorylates KDG to 2-keto-3-deoxy-6-phosphogluconate [12].

Anatomical context of C01216

• Starting from human erythrocytes, which are known to convert 3-deoxyglucosone to 2-keto-3-deoxygluconate, we have purified to near homogeneity a NAD-dependent dehydrogenase that catalyzes this last reaction at neutral pH [13].

Gene context of C01216

• Escherichia coli K-12 structural kdgT mutants exhibiting thermosensitive 2-keto-3-deoxy-D-gluconate uptake [14].
• The pathways of pectin and galacturonate catabolism in Erwinia chrysanthemi converge to form a common intermediate, 2-keto-3-deoxygluconate (KDG), which is phosphorylated by KDG kinase encoded by the kdgK gene [15].
• In Er. chrysanthemi, all genes involved in pectin degradation are specifically controlled by the KdgR repressor and are induced in the presence of a pectin catabolic product, 2-keto-3-deoxygluconate (KDG). transcription of the pectinase genes is dependent on many environmental conditions [16].

Analytical, diagnostic and therapeutic context of C01216

• Crystallization and preliminary crystallographic analysis of 2-keto-3-deoxygluconate kinase from Thermus thermophilus [17].

References