Disease relevance of DIAMINOPIMELIC ACID

• Two recent reports add to the growing list of these pattern-recognition receptors by showing that the intracellular nucleotide-binding oligomerization domain 1 (NOD1) protein recognizes a diaminopimelate-containing muropeptide, a cell-wall component of Gram-negative bacteria [1].
• An Escherichia coli K12 diaminopimelate auxotroph made invasive by cloning the invasin gene from Yersinia pseudotuberculosis transfers DNA after simple co-incubation, into a variety of mammalian cell lines [2].
• Here, we present the crystal structures of diaminopimelate (DAP) epimerase from Haemophilus influenzae with two different isomers of the irreversible inhibitor and substrate mimic aziridino-DAP at 1.35- and 1.70-A resolution [3].
• L,L-diaminopimelate aminotransferase, a trans-kingdom enzyme shared by Chlamydia and plants for synthesis of diaminopimelate/lysine [4].
• As a result, meso-lanthionine and L-allo-cystathionine were produced endogenously and incorporated in the peptidoglycan, thereby enabling E. coli strains auxotrophic for diaminopimelate to grow in its absence [5].

High impact information on DIAMINOPIMELIC ACID

• Nod1 has been described recently as a cytosolic receptor that detects specifically diaminopimelate-containing muropeptides from Gram-negative bacteria peptidoglycan [6].
• Whereas Nod2 detects GlcNAc-MurNAc dipeptide (GM-Di), Nod1 senses a unique diaminopimelate-containing GlcNAc-MurNAc tripeptide muropeptide (GM-TriDAP) found mostly in Gram-negative bacterial PGs [7].
• Structure/function studies on enzymes in the diaminopimelate pathway of bacterial cell wall biosynthesis [8].
• Organization and nucleotide sequence of the Bacillus subtilis diaminopimelate operon, a cluster of genes encoding the first three enzymes of diaminopimelate synthesis and dipicolinate synthase [9].
• E.coli AT997, a mutant host normally requiring exogenous diaminopimelate for growth, could be complemented by transformation with a plasmid bearing the gene encoding MosA [10].

Chemical compound and disease context of DIAMINOPIMELIC ACID

• In Escherichia coli, the first enzyme of the diaminopimelate and lysine pathway is dihydrodipicolinate synthetase, which is feedback-inhibited by lysine and encoded by the dapA gene [11].
• An unusual mutation results in the replacement of diaminopimelate with lanthionine in the peptidoglycan of a mutant strain of Mycobacterium smegmatis [12].
• The three-dimensional (3D) structure of Corynebacterium glutamicum diaminopimelate D-dehydrogenase in a ternary complex with NADPH and L-2-amino-6-methylene-pimelate has been solved and refined to a resolution of 2.1 A [13].
• However, this motif is not present in eukaryotic OrnDCs, the diaminopimelate decarboxylases, nor the Escherichia coli or oat arginine decarboxylases [14].
• The regulation of uridine diphosphate-N-acetylmuramyl-peptide (UDP-MurNAc-peptide) synthesis was studied by labeling Escherichia coli strains auxotrophic for lysine and diaminopimelate with [3H]diaminopimelate for 15 min under various conditions [15].

Biological context of DIAMINOPIMELIC ACID

• The synthesis of diaminopimelate decarboxylase, which catalyzes the decarboxylation of diaminopimelate into lysine, is known to be repressed by lysine and induced by diaminopimelate in Escherichia coli K12 [16].
• Diaminopimelate dehydrogenase catalyzes the only oxidative deamination of an amino acid of D configuration and must additionally distinguish between two chiral amino acid centers on the same symmetric substrate [17].
• Substrate and inhibitor binding sites in Corynebacterium glutamicum diaminopimelate dehydrogenase [18].
• As predicted from the fact that the ddp operon is activated by NtrC, synthesis of cross-links between diaminopimelate residues in the murein layer was increased under N-limiting conditions, as was the proportion of tripeptides [19].
• The deduced amino acid sequences of ORF2 and truncated ORF3 contain significant homology to bacterial lysine biosynthetic enzymes, diaminopimelate decarboxylase, and delta 1-piperidine-2,6-dicarboxylate succinyl transferase, respectively [20].

Associations of DIAMINOPIMELIC ACID with other chemical compounds

• Aspartate-beta-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the biosynthetic pathway through which bacteria, fungi, and the higher plants synthesize amino acids, including lysine and methionine and the cell wall component diaminopimelate from aspartate [21].

Gene context of DIAMINOPIMELIC ACID

• YHI9 has a fold similar to bacterial diaminopimelate epimerase, revealing a bimodular structure with an internal symmetry [22].
• Here, we show that human Nod1 specifically detects a unique diaminopimelate-containing N-acetylglucosamine-N-acetylmuramic acid (GlcNAc-MurNAc) tripeptide motif found in Gram-negative bacterial peptidoglycan, resulting in activation of the transcription factor NF-kappaB pathway [23].
• A 3.8-kb EcoRI-fragment containing the lysA gene [diaminopimelate (DAP) decarboxylase] of Bacillus subtilis has been cloned into B. subtilis phage phi 105 and its nucleotides sequenced [24].
• Characterization of a bordetella pertussis diaminopimelate (DAP) biosynthesis locus identifies dapC, a novel gene coding for an N-succinyl-L,L-DAP aminotransferase [25].
• The nucleotide sequence of a 1966 bp fragment revealed the presence of one truncated open reading frame of unknown function and that of dapE encoding N-succinyl diaminopimelate desuccinylase (EC 3.5.1.18) [26].

Analytical, diagnostic and therapeutic context of DIAMINOPIMELIC ACID

• A high-performance liquid chromatography method for the simultaneous assay of diaminopimelate epimerase and decarboxylase [27].

References