1dgd
From Proteopedia
(New page: 200px<br /><applet load="1dgd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dgd, resolution 2.8Å" /> '''AN ALKALI METAL ION S...) |
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| - | [[Image:1dgd.jpg|left|200px]]<br /><applet load="1dgd" size=" | + | [[Image:1dgd.jpg|left|200px]]<br /><applet load="1dgd" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1dgd, resolution 2.8Å" /> | caption="1dgd, resolution 2.8Å" /> | ||
'''AN ALKALI METAL ION SIZE-DEPENDENT SWITCH IN THE ACTIVE SITE STRUCTURE OF DIALKYLGLYCINE DECARBOXYLASE'''<br /> | '''AN ALKALI METAL ION SIZE-DEPENDENT SWITCH IN THE ACTIVE SITE STRUCTURE OF DIALKYLGLYCINE DECARBOXYLASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The pyridoxal 5'-phosphate-dependent enzyme dialkylglycine decarboxylase | + | The pyridoxal 5'-phosphate-dependent enzyme dialkylglycine decarboxylase (DGD) is activated by K+ and Rb+ ions, whereas Li+ and Na+ ions are inhibitory. A binding site for alkali metal ions close to the active site (site 1) was discovered in the crystal structure of DGD, and an exchange of K+ for Na+ at this site was shown to affect the conformation of two active site residues [Toney, M. D., Hohenester, E., Cowan, S. W., & Jansonius, J. N. (1993) Science 261, 756-759]. We have investigated the effects of alkali metal ions on DGD activity and have determined the crystal structures at 2.8 A resolution of DGD with Li+ and Rb+ bound at site 1. Due to the weak scattering of the Li+ ion, its position had to be modeled using information from small molecule structures. A comparison of the DGD structures with Li+, Na+, K+, and Rb+ bound at site 1 reveals a striking correlation between active site structure and enzymatic activity. The small, inhibitory ions Li+ and Na+ are accommodated by replacing two protein-derived ligands of the larger, activating ions K+ and Rb+ by a single water molecule. This actuates a two-state structural switch between active and inactive enzyme that involves a concerted reorientation of the active site residues Ser80 and Tyr301 and a small change in the quaternary structure of the DGD tetramer. An important role of the essential K+ ion in both cofactor binding and the organization of a catalytically competent active site structure is proposed. In the structure of DGD with Rb+ bound at site 1, a second Rb+ ion has partially replaced the structural Na+ ion at metal binding site 2 on the surface of the DGD molecule, without significantly altering the protein structure. In contrast to Na+, the Rb+ ion is bound with unfavorable geometry, and it is proposed that the rigid site 2 structure results in a pronounced selectivity for Na+ ions. |
==About this Structure== | ==About this Structure== | ||
| - | 1DGD 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, LI, PLP and MES 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:// | + | 1DGD 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=LI:'>LI</scene>, <scene name='pdbligand=PLP:'>PLP</scene> and <scene name='pdbligand=MES:'>MES</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=1DGD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hohenester, E.]] | [[Category: Hohenester, E.]] | ||
| - | [[Category: Jansonius, J | + | [[Category: Jansonius, J N.]] |
[[Category: LI]] | [[Category: LI]] | ||
[[Category: MES]] | [[Category: MES]] | ||
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[[Category: lyase]] | [[Category: lyase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:16:27 2008'' |
Revision as of 10:16, 21 February 2008
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AN ALKALI METAL ION SIZE-DEPENDENT SWITCH IN THE ACTIVE SITE STRUCTURE OF DIALKYLGLYCINE DECARBOXYLASE
Overview
The pyridoxal 5'-phosphate-dependent enzyme dialkylglycine decarboxylase (DGD) is activated by K+ and Rb+ ions, whereas Li+ and Na+ ions are inhibitory. A binding site for alkali metal ions close to the active site (site 1) was discovered in the crystal structure of DGD, and an exchange of K+ for Na+ at this site was shown to affect the conformation of two active site residues [Toney, M. D., Hohenester, E., Cowan, S. W., & Jansonius, J. N. (1993) Science 261, 756-759]. We have investigated the effects of alkali metal ions on DGD activity and have determined the crystal structures at 2.8 A resolution of DGD with Li+ and Rb+ bound at site 1. Due to the weak scattering of the Li+ ion, its position had to be modeled using information from small molecule structures. A comparison of the DGD structures with Li+, Na+, K+, and Rb+ bound at site 1 reveals a striking correlation between active site structure and enzymatic activity. The small, inhibitory ions Li+ and Na+ are accommodated by replacing two protein-derived ligands of the larger, activating ions K+ and Rb+ by a single water molecule. This actuates a two-state structural switch between active and inactive enzyme that involves a concerted reorientation of the active site residues Ser80 and Tyr301 and a small change in the quaternary structure of the DGD tetramer. An important role of the essential K+ ion in both cofactor binding and the organization of a catalytically competent active site structure is proposed. In the structure of DGD with Rb+ bound at site 1, a second Rb+ ion has partially replaced the structural Na+ ion at metal binding site 2 on the surface of the DGD molecule, without significantly altering the protein structure. In contrast to Na+, the Rb+ ion is bound with unfavorable geometry, and it is proposed that the rigid site 2 structure results in a pronounced selectivity for Na+ ions.
About this Structure
1DGD 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
An alkali metal ion size-dependent switch in the active site structure of dialkylglycine decarboxylase., Hohenester E, Keller JW, Jansonius JN, Biochemistry. 1994 Nov 22;33(46):13561-70. PMID:7947767
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