1f06: Difference between revisions

Revision as of 13:33, 21 February 2008

THREE DIMENSIONAL STRUCTURE OF THE TERNARY COMPLEX OF CORYNEBACTERIUM GLUTAMICUM DIAMINOPIMELATE DEHYDROGENASE NADPH-L-2-AMINO-6-METHYLENE-PIMELATE

OverviewOverview

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.

About this StructureAbout this Structure

1F06 is a Single protein structure of sequence from Corynebacterium glutamicum with and as ligands. Active as Diaminopimelate dehydrogenase, with EC number 1.4.1.16 Full crystallographic information is available from OCA.

ReferenceReference

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

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-[[Image:1f06.gif|left|200px]]<br /><applet load="1f06" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1f06.gif|left|200px]]<br /><applet load="1f06" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1f06, resolution 2.1&Aring;" />
 '''THREE DIMENSIONAL STRUCTURE OF THE TERNARY COMPLEX OF CORYNEBACTERIUM GLUTAMICUM DIAMINOPIMELATE DEHYDROGENASE NADPH-L-2-AMINO-6-METHYLENE-PIMELATE'''<br />
 ==Overview==
-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 (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.
 ==About this Structure==
-F06 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 NDP and 2NP as [http://en.wikipedia.org/wiki/ligands ligands]. 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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1F06 OCA].
+F06 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 <scene name='pdbligand=NDP:'>NDP</scene> and <scene name='pdbligand=2NP:'>2NP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F06 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Diaminopimelate dehydrogenase]]
 [[Category: Single protein]]
-[[Category: Blanchard, J.S.]]
+[[Category: Blanchard, J S.]]
-[[Category: Caplan, J.F.]]
+[[Category: Caplan, J F.]]
 [[Category: Cirilli, M.]]
 [[Category: Scapin, G.]]
 [[Category: Sutherland, A.]]
-[[Category: Vederas, J.C.]]
+[[Category: Vederas, J C.]]
 [[Category: 2NP]]
 [[Category: NDP]]
 [[Category: enzyme-nadph-inhibitor ternary complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 14:29:21 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:33:24 2008''