Structural highlights
Function
[DAPDH_CORGL] Catalyzes the reversible NADPH-dependent reductive amination of L-2-amino-6-oxopimelate, the acyclic form of L-tetrahydrodipicolinate, to generate the meso compound, D,L-2,6-diaminopimelate. Probably plays a role in lysine biosynthesis. Exhibits a high substrate specificity for meso-2,6-diaminopimelate, since L,L-2,6-diaminopimelate, D,D-2,6-diaminopimelate, L-glutamate, L-alanine, L-leucine, L-valine, L-aspartate, L-threonine, L-homoserine, L-methionine, L-lysine, L-serine, L-phenylalanine, L-tyrosine, L-tryptophan, L-ornithine, L-histidine, L-arginine, D-glutamate, and D-alanine are not substrates for the oxidative deamination reaction. Can use NAD(+) only poorly since the activity observed in the presence of NAD(+) is about 3% of that with NADP(+).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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. L-2-Amino-6-methylene-pimelate was recently synthesized and shown to be a potent competitive inhibitor (5 microM) vs. meso-diaminopimelate of the Bacillus sphaericus dehydrogenase (Sutherland et al., 1999). Diaminopimelate dehydrogenase catalyzes the reversible NADP+ -dependent oxidation of the D-amino acid stereocenter of mesodiaminopimelate, and is the only enzyme known to catalyze the oxidative deamination of a D-amino acid. The enzyme is involved in the biosynthesis of meso-diaminopimelate and L-lysine from L-aspartate, a biosynthetic pathway of considerable interest because it is essential for growth of certain bacteria. The dehydrogenase is found in a limited number of species of bacteria, as opposed to the alternative succinylase and acetylase pathways that are widely distributed in bacteria and plants. The structure of the ternary complex reported here provides a structural rationale for the nature and potency of the inhibition exhibited by the unsaturated L-2-amino-6-methylene-pimelate against the dehydrogenase. In particular, we compare the present structure with other structures containing either bound substrate, meso-diaminopimelate, or a conformationally restricted isoxazoline inhibitor. We have identified a significant interaction between the alpha-L-amino group of the unsaturated inhibitor and the indole ring of Trp144 that may account for the tight binding of this inhibitor.
The three-dimensional structure of the ternary complex of Corynebacterium glutamicum diaminopimelate dehydrogenase-NADPH-L-2-amino-6-methylene-pimelate.,Cirilli M, Scapin G, Sutherland A, Vederas JC, Blanchard JS Protein Sci. 2000 Oct;9(10):2034-7. PMID:11106178[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Reddy SG, Scapin G, Blanchard JS. Expression, purification, and crystallization of meso-diaminopimelate dehydrogenase from Corynebacterium glutamicum. Proteins. 1996 Aug;25(4):514-6. PMID:8865347 doi:http://dx.doi.org/10.1002/prot.12
- ↑ Reddy SG, Scapin G, Blanchard JS. Expression, purification, and crystallization of meso-diaminopimelate dehydrogenase from Corynebacterium glutamicum. Proteins. 1996 Aug;25(4):514-6. PMID:8865347 doi:http://dx.doi.org/10.1002/prot.12
- ↑ Cirilli M, Scapin G, Sutherland A, Vederas JC, Blanchard JS. The three-dimensional structure of the ternary complex of Corynebacterium glutamicum diaminopimelate dehydrogenase-NADPH-L-2-amino-6-methylene-pimelate. Protein Sci. 2000 Oct;9(10):2034-7. PMID:11106178
