3dap: Difference between revisions
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[[Image:3dap.gif|left|200px]]< | [[Image:3dap.gif|left|200px]] | ||
'''C. GLUTAMICUM DAP DEHYDROGENASE IN COMPLEX WITH NADP+ AND THE INHIBITOR 5S-ISOXAZOLINE''' | {{Structure | ||
|PDB= 3dap |SIZE=350|CAPTION= <scene name='initialview01'>3dap</scene>, resolution 2.2Å | |||
|SITE= <scene name='pdbsite=INH:Inhibitor+Binding+Site+In+Second+Molecule'>INH</scene>, <scene name='pdbsite=N1:Nadp++Binding+Site+In+First+Molecule'>N1</scene> and <scene name='pdbsite=N2:Nadp++Binding+Site+In+Second+Molecule'>N2</scene> | |||
|LIGAND= <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene> and <scene name='pdbligand=DA3:(2S,5',S)-2-AMINO-3-(3-CARBOXY-2-ISOXAZOLIN-5-YL)PROPANOIC ACID'>DA3</scene> | |||
|ACTIVITY= [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] | |||
|GENE= DAPDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1718 Corynebacterium glutamicum]) | |||
}} | |||
'''C. GLUTAMICUM DAP DEHYDROGENASE IN COMPLEX WITH NADP+ AND THE INHIBITOR 5S-ISOXAZOLINE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
3DAP is a [ | 3DAP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Corynebacterium_glutamicum Corynebacterium glutamicum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DAP OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/9521647 9521647] | ||
[[Category: Corynebacterium glutamicum]] | [[Category: Corynebacterium glutamicum]] | ||
[[Category: Diaminopimelate dehydrogenase]] | [[Category: Diaminopimelate dehydrogenase]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:04:23 2008'' | ||
Revision as of 20:04, 20 March 2008
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| , resolution 2.2Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , and | ||||||
| Ligands: | and | ||||||
| Gene: | DAPDH (Corynebacterium glutamicum) | ||||||
| Activity: | Diaminopimelate dehydrogenase, with EC number 1.4.1.16 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
C. GLUTAMICUM DAP DEHYDROGENASE IN COMPLEX WITH NADP+ AND THE INHIBITOR 5S-ISOXAZOLINE
OverviewOverview
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 StructureAbout this Structure
3DAP is a Single protein structure of sequence from Corynebacterium glutamicum. Full crystallographic information is available from OCA.
ReferenceReference
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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