2dap
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The three-dimensional structures of Corynebacterium glutamicum, diaminopimelate dehydrogenase as a binary complex with the substrate, meso-diaminopimelate (meso-DAP) and a ternary complex with NADP+ and an, isoxazoline inhibitor [Abbot, S.D., Lane-Bell, P., Kanwar, P.S.S., and, Vederas, J. C. (1994) J. Am. Chem. Soc. 116, 6513-6520] have been solved, and refined against X-ray diffraction data to 2.2 A. Diaminopimelate, dehydrogenase is a homodimer of approximately 35,000 molecular weight, subunits and is the only dehydrogenase present in the bacterial, diaminopimelate/lysine biosynthetic pathway. Inhibitors of the enzymes of, L-lysine biosynthesis have been proposed as potential antibiotics or, herbicides, since mammals lack this metabolic pathway. Diaminopimelate, dehydrogenase catalyzes ... | + | The three-dimensional structures of Corynebacterium glutamicum, diaminopimelate dehydrogenase as a binary complex with the substrate, meso-diaminopimelate (meso-DAP) and a ternary complex with NADP+ and an, isoxazoline inhibitor [Abbot, S.D., Lane-Bell, P., Kanwar, P.S.S., and, Vederas, J. C. (1994) J. Am. Chem. Soc. 116, 6513-6520] have been solved, and refined against X-ray diffraction data to 2.2 A. Diaminopimelate, dehydrogenase is a homodimer of approximately 35,000 molecular weight, subunits and is the only dehydrogenase present in the bacterial, diaminopimelate/lysine biosynthetic pathway. Inhibitors of the enzymes of, L-lysine biosynthesis have been proposed as potential antibiotics or, herbicides, since mammals lack this metabolic pathway. Diaminopimelate, dehydrogenase catalyzes the unique, reversible, pyridine, dinucleotide-dependent oxidative deamination of the D-amino acid, stereocenter of meso-diaminopimelate to generate L-2-amino-6-oxopimelate., The enzyme is absolutely specific for the meso stereoisomer of DAP and, must distinguish between two opposite chiral amino acid centers on the, same symmetric substrate. The determination of the three-dimensional, structure of the enzyme--meso-diaminopimelate complex allows a description, of the molecular basis of this stereospecific discrimination. The, substrate is bound in an elongated cavity, in which the distribution of, residues that act as hydrogen bond donors or acceptors defines a single, orientation in which the substrate may bind in order to position the, D-amino acid center of meso-DAP near the oxidized nucleotide. The, previously described isoxazoline inhibitor binds at the same site as DAP, but has its L-amino acid center positioned where the D-amino acid center, of meso-DAP would normally be located, thereby generating a nonproductive, inhibitor complex. The relative positions of the N-terminal dinucleotide, and C-terminal substrate-binding domains in the diaminopimelate, dehydrogenase--NADP+, diaminopimelate dehydrogenase--DAP, and, diaminopimelate dehydrogenase--NADP(+)--inhibitor complexes confirm our, previous observations that the enzyme undergoes significant conformational, changes upon binding of both dinucleotide and substrate. |
==About this Structure== | ==About this Structure== | ||
| - | 2DAP is a | + | 2DAP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Corynebacterium_glutamicum Corynebacterium glutamicum] with API as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Diaminopimelate_dehydrogenase Diaminopimelate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.1.16 1.4.1.16] Structure known Active Site: DAP. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2DAP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:58:15 2007'' |
Revision as of 12:52, 5 November 2007
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C. GLUTAMICUM DAP DEHYDROGENASE IN COMPLEX WITH DAP
Overview
The three-dimensional structures of Corynebacterium glutamicum, diaminopimelate dehydrogenase as a binary complex with the substrate, meso-diaminopimelate (meso-DAP) and a ternary complex with NADP+ and an, isoxazoline inhibitor [Abbot, S.D., Lane-Bell, P., Kanwar, P.S.S., and, Vederas, J. C. (1994) J. Am. Chem. Soc. 116, 6513-6520] have been solved, and refined against X-ray diffraction data to 2.2 A. Diaminopimelate, dehydrogenase is a homodimer of approximately 35,000 molecular weight, subunits and is the only dehydrogenase present in the bacterial, diaminopimelate/lysine biosynthetic pathway. Inhibitors of the enzymes of, L-lysine biosynthesis have been proposed as potential antibiotics or, herbicides, since mammals lack this metabolic pathway. Diaminopimelate, dehydrogenase catalyzes the unique, reversible, pyridine, dinucleotide-dependent oxidative deamination of the D-amino acid, stereocenter of meso-diaminopimelate to generate L-2-amino-6-oxopimelate., The enzyme is absolutely specific for the meso stereoisomer of DAP and, must distinguish between two opposite chiral amino acid centers on the, same symmetric substrate. The determination of the three-dimensional, structure of the enzyme--meso-diaminopimelate complex allows a description, of the molecular basis of this stereospecific discrimination. The, substrate is bound in an elongated cavity, in which the distribution of, residues that act as hydrogen bond donors or acceptors defines a single, orientation in which the substrate may bind in order to position the, D-amino acid center of meso-DAP near the oxidized nucleotide. The, previously described isoxazoline inhibitor binds at the same site as DAP, but has its L-amino acid center positioned where the D-amino acid center, of meso-DAP would normally be located, thereby generating a nonproductive, inhibitor complex. The relative positions of the N-terminal dinucleotide, and C-terminal substrate-binding domains in the diaminopimelate, dehydrogenase--NADP+, diaminopimelate dehydrogenase--DAP, and, diaminopimelate dehydrogenase--NADP(+)--inhibitor complexes confirm our, previous observations that the enzyme undergoes significant conformational, changes upon binding of both dinucleotide and substrate.
About this Structure
2DAP is a Single protein structure of sequence from Corynebacterium glutamicum with API as ligand. Active as Diaminopimelate dehydrogenase, with EC number 1.4.1.16 Structure known Active Site: DAP. Full crystallographic information is available from OCA.
Reference
Substrate and inhibitor binding sites in Corynebacterium glutamicum diaminopimelate dehydrogenase., Scapin G, Cirilli M, Reddy SG, Gao Y, Vederas JC, Blanchard JS, Biochemistry. 1998 Mar 10;37(10):3278-85. PMID:9521647
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