3r5d

Pseudomonas aeruginosa DapD (PA3666) apoprotein

spinqualitylabelsall models 3r5d, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3r5d is a 6 chain structure with sequence from "bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL Related: 3r5a, 3r5b, 3r5c Gene: dapD, PA3666 ("Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885) Activity: 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase, with EC number 2.3.1.117 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DAPD_PSEAE] Catalyzes the conversion of the cyclic tetrahydrodipicolinate (THDP) into the acyclic N-succinyl-L-2-amino-6-oxopimelate using succinyl-CoA. It can only accept L-2 aminopimelate as substrate. Publication Abstract from PubMed The diaminopimelic acid pathway of lysine biosynthesis has been suggested to provide attractive targets for the development of novel antibacterial drugs. Here we report the characterization of two enzymes from this pathway in the human pathogen Pseudomonas aeruginosa, utilizing structural biology, biochemistry and genetics. We show that tetrahydrodipicolinate N-succinyltransferase (DapD) from P. aeruginosa is specific for the L-stereoisomer of the amino substrate L-2-aminopimelate, and its D-enantiomer acts as a weak inhibitor. The crystal structures of this enzyme with L-2-aminopimelate and D-2-aminopimelate, respectively, reveal that both compounds bind at the same site of the enzyme. Comparison of the binding interactions of these ligands in the enzyme active site suggests misalignment of the amino group of D-2-aminopimelate for nucleophilic attack on the succinate moiety of the co-substrate succinyl-CoA as the structural basis of specificity and inhibition. P. aeruginosa mutants where the dapA gene had been deleted were viable and able to grow in a mouse lung infection model, suggesting that DapA is not an optimal target for drug development against this organism. Structure-based sequence alignments, based on the DapA crystal structure determined to 1.6 A resolution revealed the presence of two homologues, PA0223 and PA4188, in P. aeruginosa that could substitute for DapA in the P. aeruginosa PAO1DeltadapA mutant. In vitro experiments using recombinant PA0223 protein could however not detect any DapA activity. Tetrahydrodipicolinate N-succinyltransferase and dihydrodipicolinate synthase from Pseudomonas aeruginosa: structure analysis and gene deletion.,Schnell R, Oehlmann W, Sandalova T, Braun Y, Huck C, Maringer M, Singh M, Schneider G PLoS One. 2012;7(2):e31133. doi: 10.1371/journal.pone.0031133. Epub 2012 Feb 16. PMID:22359568 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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