1d7v
From Proteopedia
(New page: 200px<br /><applet load="1d7v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d7v, resolution 2.80Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1d7v.jpg|left|200px]]<br /><applet load="1d7v" size=" | + | [[Image:1d7v.jpg|left|200px]]<br /><applet load="1d7v" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1d7v, resolution 2.80Å" /> | caption="1d7v, resolution 2.80Å" /> | ||
'''CRYSTAL STRUCTURE OF THE COMPLEX OF 2,2-DIALKYLGLYCINE DECARBOXYLASE WITH NMA'''<br /> | '''CRYSTAL STRUCTURE OF THE COMPLEX OF 2,2-DIALKYLGLYCINE DECARBOXYLASE WITH NMA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structures of four inhibitor complexes of dialkylglycine | + | The crystal structures of four inhibitor complexes of dialkylglycine decarboxylase are reported. The enzyme does not undergo a domain closure, as does aspartate aminotransferase, upon inhibitor binding. Two active-site conformations have been observed in previous structures that differ in alkali metal ion content, and two active-site conformations have been shown to coexist in solution when a single type of metal ion is present. There is no indication of coexisting conformers in the structures reported here or in the previously reported structures, and the observed conformation is that expected based on the presence of potassium in the enzyme. Thus, although two active-site conformations coexist in solution, a single conformation, corresponding to the more active enzyme, predominates in the crystal. The structure of 1-aminocyclopropane-1-carboxylate bound in the active site shows the aldimine double bond to the pyridoxal phosphate cofactor to be fully out of the plane of the coenzyme ring, whereas the Calpha-CO2(-) bond lies close to it. This provides an explanation for the observed lack of decarboxylation reactivity with this amino acid. The carboxylate groups of both 1-aminocyclopropane-1-carboxylate and 5'-phosphopyridoxyl-2-methylalanine interact with Ser215 and Arg406 as previously proposed. This demonstrates structurally that alternative binding modes, which constitute substrate inhibition, occur in the decarboxylation half-reaction. The structures of d and l-cycloserine bound to the active-site show that the l-isomer is deprotonated at C(alpha), presumably by Lys272, while the d-isomer is not. This difference explains the approximately 3000-fold greater potency of the l versus the d-isomer as a competitive inhibitor of dialkylglycine decarboxylase. |
==About this Structure== | ==About this Structure== | ||
| - | 1D7V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Burkholderia_cepacia Burkholderia cepacia] with NA, K and NMA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/2,2-dialkylglycine_decarboxylase_(pyruvate) 2,2-dialkylglycine decarboxylase (pyruvate)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.64 4.1.1.64] Full crystallographic information is available from [http:// | + | 1D7V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Burkholderia_cepacia Burkholderia cepacia] with <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=K:'>K</scene> and <scene name='pdbligand=NMA:'>NMA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/2,2-dialkylglycine_decarboxylase_(pyruvate) 2,2-dialkylglycine decarboxylase (pyruvate)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.64 4.1.1.64] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D7V OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Burkholderia cepacia]] | [[Category: Burkholderia cepacia]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Jansonius, J | + | [[Category: Jansonius, J N.]] |
[[Category: Keller, J.]] | [[Category: Keller, J.]] | ||
| - | [[Category: Malashkevich, V | + | [[Category: Malashkevich, V N.]] |
[[Category: Strop, P.]] | [[Category: Strop, P.]] | ||
| - | [[Category: Toney, M | + | [[Category: Toney, M D.]] |
[[Category: K]] | [[Category: K]] | ||
[[Category: NA]] | [[Category: NA]] | ||
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[[Category: enzyme complexes]] | [[Category: enzyme complexes]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:13:53 2008'' |
Revision as of 10:13, 21 February 2008
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CRYSTAL STRUCTURE OF THE COMPLEX OF 2,2-DIALKYLGLYCINE DECARBOXYLASE WITH NMA
Overview
The crystal structures of four inhibitor complexes of dialkylglycine decarboxylase are reported. The enzyme does not undergo a domain closure, as does aspartate aminotransferase, upon inhibitor binding. Two active-site conformations have been observed in previous structures that differ in alkali metal ion content, and two active-site conformations have been shown to coexist in solution when a single type of metal ion is present. There is no indication of coexisting conformers in the structures reported here or in the previously reported structures, and the observed conformation is that expected based on the presence of potassium in the enzyme. Thus, although two active-site conformations coexist in solution, a single conformation, corresponding to the more active enzyme, predominates in the crystal. The structure of 1-aminocyclopropane-1-carboxylate bound in the active site shows the aldimine double bond to the pyridoxal phosphate cofactor to be fully out of the plane of the coenzyme ring, whereas the Calpha-CO2(-) bond lies close to it. This provides an explanation for the observed lack of decarboxylation reactivity with this amino acid. The carboxylate groups of both 1-aminocyclopropane-1-carboxylate and 5'-phosphopyridoxyl-2-methylalanine interact with Ser215 and Arg406 as previously proposed. This demonstrates structurally that alternative binding modes, which constitute substrate inhibition, occur in the decarboxylation half-reaction. The structures of d and l-cycloserine bound to the active-site show that the l-isomer is deprotonated at C(alpha), presumably by Lys272, while the d-isomer is not. This difference explains the approximately 3000-fold greater potency of the l versus the d-isomer as a competitive inhibitor of dialkylglycine decarboxylase.
About this Structure
1D7V is a Single protein structure of sequence from Burkholderia cepacia with , and as ligands. Active as 2,2-dialkylglycine decarboxylase (pyruvate), with EC number 4.1.1.64 Full crystallographic information is available from OCA.
Reference
Crystal structures of dialkylglycine decarboxylase inhibitor complexes., Malashkevich VN, Strop P, Keller JW, Jansonius JN, Toney MD, J Mol Biol. 1999 Nov 19;294(1):193-200. PMID:10556038
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