PDBsum entry 1dgd

Lyase

PDB id: 1dgd

Contents

Protein chain

431 a.a.

Ligands

PLP

MES

Metals

_NA

_LI

Waters ×99

References listed in PDB file

Key reference

• Title: An alkali metal ion size-Dependent switch in the active site structure of dialkylglycine decarboxylase.
• Authors: E.Hohenester, J.W.Keller, J.N.Jansonius.
• Ref.: Biochemistry, 1994, 33, 13561-13570. [DOI no: 10.1021/bi00250a008]
• PubMed id: 7947767

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.

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., & 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.

Secondary reference #1

• Title: Dialkylglycine decarboxylase structure: bifunctional active site and alkali metal sites.
• Authors: M.D.Toney, E.Hohenester, S.W.Cowan, J.N.Jansonius.
• Ref.: Science, 1993, 261, 756-759. [DOI no: 10.1126/science.8342040]
• PubMed id: 8342040

Secondary reference #2

• Title: Pseudomonas cepacia 2,2-Dialkylglycine decarboxylase. Sequence and expression in escherichia coli of structural and repressor genes.
• Authors: J.W.Keller, K.B.Baurick, G.C.Rutt, M.V.O'Malley, N.L.Sonafrank, R.A.Reynolds, L.O.Ebbesson, F.F.Vajdos.
• Ref.: J Biol Chem, 1990, 265, 5531-5539.
• PubMed id: 2180928