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| AN ALKALI-METAL ION SIZE-DEPENDENT SWITCH IN THE ACTIVE-SITE STRUCTURE OF DIALKYLGLYCINE DECARBOXYLASE |
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| Author(s): HOHENESTER E, KELLER JW, JANSONIUS JN |
| Source: BIOCHEMISTRY Volume: 33 Issue: 46 Pages: 13561-13570 Published: NOV 22 1994 |
| Times Cited: 47 References: 31 |
| Abstract: 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., and 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 Angstrom 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV BASEL, BIOZENTRUM, DEPT BIOL STRUCT, CH-4056 BASEL, SWITZERLAND
2. UNIV ALASKA, DEPT CHEM, FAIRBANKS, AK 99775 USA |
| Publisher: AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: PT485 |
| ISSN: 0006-2960 |
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