1kgt: Difference between revisions

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Crystal Structure of Tetrahydrodipicolinate N-Succinyltransferase in Complex with Pimelate and Succinyl-CoA

OverviewOverview

Tetrahydrodipicolinate N-succinyltransferase (DapD) catalyzes the succinyl-CoA-dependent acylation of L-2-amino-6-oxopimelate to 2-N-succinyl-6-oxopimelate as part of the succinylase branch of the meso-diaminopimelate/lysine biosynthetic pathway of bacteria, blue-green algae, and plants. This pathway provides meso-diaminopimelate as a building block for cell wall peptidoglycan in most bacteria, and is regarded as a target pathway for antibacterial agents. We have solved the X-ray crystal structures of DapD in ternary complexes with pimelate/succinyl-CoA and L-2-aminopimelate with the nonreactive cofactor analog, succinamide-CoA. These structures define the binding conformation of the cofactor succinyl group and its interactions with the enzyme and place its thioester carbonyl carbon in close proximity to the nucleophilic 2-amino group of the acceptor, in support of a direct attack ternary complex mechanism. The acyl group specificity differences between homologous tetrahydrodipicolinate N-acetyl- and N-succinyltransferases can be rationalized with reference to at least three amino acids that interact with or give accessible active site volume to the cofactor succinyl group. These residues account at least in part for the substrate specificity that commits metabolic intermediates to either the succinylase or acetylase branches of the meso-diaminopimelate/lysine biosynthetic pathway.

About this StructureAbout this Structure

1KGT is a Single protein structure of sequence from Mycobacterium bovis with and as ligands. Active as 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase, with EC number 2.3.1.117 Full crystallographic information is available from OCA.

ReferenceReference

Acyl group specificity at the active site of tetrahydridipicolinate N-succinyltransferase., Beaman TW, Vogel KW, Drueckhammer DG, Blanchard JS, Roderick SL, Protein Sci. 2002 Apr;11(4):974-9. PMID:11910040

Page seeded by OCA on Thu Feb 21 13:34:01 2008

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OCA

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-[[Image:1kgt.gif|left|200px]]<br /><applet load="1kgt" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1kgt.gif|left|200px]]<br /><applet load="1kgt" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1kgt, resolution 2.3&Aring;" />
 '''Crystal Structure of Tetrahydrodipicolinate N-Succinyltransferase in Complex with Pimelate and Succinyl-CoA'''<br />
 ==Overview==
-Tetrahydrodipicolinate N-succinyltransferase (DapD) catalyzes the, succinyl-CoA-dependent acylation of L-2-amino-6-oxopimelate to, 2-N-succinyl-6-oxopimelate as part of the succinylase branch of the, meso-diaminopimelate/lysine biosynthetic pathway of bacteria, blue-green, algae, and plants. This pathway provides meso-diaminopimelate as a, building block for cell wall peptidoglycan in most bacteria, and is, regarded as a target pathway for antibacterial agents. We have solved the, X-ray crystal structures of DapD in ternary complexes with, pimelate/succinyl-CoA and L-2-aminopimelate with the nonreactive cofactor, analog, succinamide-CoA. These structures define the binding conformation, of the cofactor succinyl group and its interactions with the enzyme and, place its thioester carbonyl carbon in close proximity to the nucleophilic, 2-amino group of the acceptor, in support of a direct attack ternary, complex mechanism. The acyl group specificity differences between, homologous tetrahydrodipicolinate N-acetyl- and N-succinyltransferases can, be rationalized with reference to at least three amino acids that interact, with or give accessible active site volume to the cofactor succinyl group., These residues account at least in part for the substrate specificity that, commits metabolic intermediates to either the succinylase or acetylase, branches of the meso-diaminopimelate/lysine biosynthetic pathway.
+Tetrahydrodipicolinate N-succinyltransferase (DapD) catalyzes the succinyl-CoA-dependent acylation of L-2-amino-6-oxopimelate to 2-N-succinyl-6-oxopimelate as part of the succinylase branch of the meso-diaminopimelate/lysine biosynthetic pathway of bacteria, blue-green algae, and plants. This pathway provides meso-diaminopimelate as a building block for cell wall peptidoglycan in most bacteria, and is regarded as a target pathway for antibacterial agents. We have solved the X-ray crystal structures of DapD in ternary complexes with pimelate/succinyl-CoA and L-2-aminopimelate with the nonreactive cofactor analog, succinamide-CoA. These structures define the binding conformation of the cofactor succinyl group and its interactions with the enzyme and place its thioester carbonyl carbon in close proximity to the nucleophilic 2-amino group of the acceptor, in support of a direct attack ternary complex mechanism. The acyl group specificity differences between homologous tetrahydrodipicolinate N-acetyl- and N-succinyltransferases can be rationalized with reference to at least three amino acids that interact with or give accessible active site volume to the cofactor succinyl group. These residues account at least in part for the substrate specificity that commits metabolic intermediates to either the succinylase or acetylase branches of the meso-diaminopimelate/lysine biosynthetic pathway.
 ==About this Structure==
-KGT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_bovis Mycobacterium bovis] with PML and SCA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/2,3,4,5-tetrahydropyridine-2,6-dicarboxylate_N-succinyltransferase 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.117 2.3.1.117] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KGT OCA].
+KGT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_bovis Mycobacterium bovis] with <scene name='pdbligand=PML:'>PML</scene> and <scene name='pdbligand=SCA:'>SCA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/2,3,4,5-tetrahydropyridine-2,6-dicarboxylate_N-succinyltransferase 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.117 2.3.1.117] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KGT OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Mycobacterium bovis]]
 [[Category: Single protein]]
-[[Category: Beaman, T.W.]]
+[[Category: Beaman, T W.]]
-[[Category: Blanchard, J.S.]]
+[[Category: Blanchard, J S.]]
-[[Category: Drueckhammer, D.G.]]
+[[Category: Drueckhammer, D G.]]
-[[Category: Roderick, S.L.]]
+[[Category: Roderick, S L.]]
-[[Category: Vogel, K.W.]]
+[[Category: Vogel, K W.]]
 [[Category: PML]]
 [[Category: SCA]]
 [[Category: left-handed parallel beta helix]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 19:12:12 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:34:01 2008''