1D7U

Crystal structure of the complex of 2,2-dialkylglycine decarboxylase with LCS

Summary for 1D7U

• Entry DOI: 10.2210/pdb1d7u/pdb
• Related: 1D7R 1D7S 1D7V
• Descriptor: PROTEIN (2,2-DIALKYLGLYCINE DECARBOXYLASE (PYRUVATE)), SODIUM ION, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: enzyme complexes, catalytic mechanism, decarboxylation inhibitor, lyase
• Biological source: Burkholderia cepacia
• Total number of polymer chains: 1
• Total formula weight: 46888.63

Authors

Malashkevich, V.N.,Toney, M.D.,Strop, P.,Keller, J.,Jansonius, J.N. (deposition date: 1999-10-19, release date: 1999-11-19, Last modification date: 2023-08-09)

Primary citation

Malashkevich, V.N.,Strop, P.,Keller, J.W.,Jansonius, J.N.,Toney, M.D.
Crystal structures of dialkylglycine decarboxylase inhibitor complexes.
J.Mol.Biol., 294:193-200, 1999

PubMed Abstract: 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.

PubMed: 10556038
DOI: 10.1006/jmbi.1999.3254

Experimental method

X-RAY DIFFRACTION (1.95 Å)