Disease relevance of CPD-622

• Significant sequence similarities were found also to the prpBCDE operons of Escherichia coli and Salmonella enterica, which are known to encode enzymes of the propionate-degrading 2-methylcitrate pathway [1].
• The acnD genes of Shewenella oneidensis and Vibrio cholerae encode a new Fe/S-dependent 2-methylcitrate dehydratase enzyme that requires prpF function in vivo [2].
• Identification of two prpDBC gene clusters in Corynebacterium glutamicum and their involvement in propionate degradation via the 2-methylcitrate cycle [1].
• Accumulation of 2-methylcitrate inside the mitochondrion, therefore, might lead to inhibition of enzymes in the citric acid cycle and thereby contribute to the ketogenesis and hypoglycemia seen under these conditions [3].
• These compounds have been used to crystallize an enzyme encoded by the Salmonella enterica prpD gene that catalyzes the dehydration of 2-methylcitrate to form 2-methyl-cis-aconitate [4].

High impact information on CPD-622

• Deletion of the 5' 615-bp portion of the prpR gene resulted in a PrpR(c) mutant protein that activated prpBCDE transcription regardless of the ability of the strain to synthesize 2-methylcitrate, the putative coactivator of PrpR [5].
• Acetyl-CoA carboxylase was activated by 2-methylcitrate with a Ka of 2.8 mM [3].
• Phosphofructokinase was also inhibited by 2-methylcitrate with 50% inhibition achieved at 1 mM [3].
• 2-Methylcitrate was not a substrate for ATP-citrate lyase [3].
• The core region of the element contains a large set of putative genes, whose products show similarity to enzymes involved in central intermediary metabolism (e.g. tricarboxylic acid cycle or 2-methylcitrate cycle), transporters, transcriptional regulators and conserved proteins of unknown function [6].

Biological context of CPD-622

• On the other hand, we identified five cadmium-binding proteins: 2-methylcitrate dehydratase, phosphate peripalsmic binding protein, inosine-5'-monophosphate dehydrogenase/guanosine-5'-monophosphate reductase, inositol monophosphatase, and lytic murein transglycosylase [7].

References