3ANV

Crystal structure of D-serine dehydratase from chicken kidney (2,3-DAP complex)

Summary for 3ANV

• Entry DOI: 10.2210/pdb3anv/pdb
• Related: 3ANU
• Descriptor: D-serine dehydratase, PYRIDOXAL-5'-PHOSPHATE, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: plp-dependent fold-type iii enzyme, d-serine dehydratase, plp binding, zinc binding, lyase
• Biological source: Gallus gallus (chicken)
• Total number of polymer chains: 1
• Total formula weight: 40901.35

Authors

Tanaka, H.,Senda, M.,Venugopalan, N.,Yamamoto, A.,Senda, T.,Ishida, T.,Horiike, K. (deposition date: 2010-09-09, release date: 2011-06-15, Last modification date: 2024-03-13)

Primary citation

Tanaka, H.,Senda, M.,Venugopalan, N.,Yamamoto, A.,Senda, T.,Ishida, T.,Horiike, K.
Crystal structure of a zinc-dependent D-serine dehydratase from chicken kidney
J.Biol.Chem., 286:27548-27558, 2011

PubMed Abstract: D-serine is a physiological co-agonist of the N-methyl-D-aspartate receptor. It regulates excitatory neurotransmission, which is important for higher brain functions in vertebrates. In mammalian brains, D-amino acid oxidase degrades D-serine. However, we have found recently that in chicken brains the oxidase is not expressed and instead a D-serine dehydratase degrades D-serine. The primary structure of the enzyme shows significant similarities to those of metal-activated D-threonine aldolases, which are fold-type III pyridoxal 5'-phosphate (PLP)-dependent enzymes, suggesting that it is a novel class of D-serine dehydratase. In the present study, we characterized the chicken enzyme biochemically and also by x-ray crystallography. The enzyme activity on D-serine decreased 20-fold by EDTA treatment and recovered nearly completely by the addition of Zn(2+). None of the reaction products that would be expected from side reactions of the PLP-D-serine Schiff base were detected during the >6000 catalytic cycles of dehydration, indicating high reaction specificity. We have determined the first crystal structure of the D-serine dehydratase at 1.9 Å resolution. In the active site pocket, a zinc ion that coordinates His(347) and Cys(349) is located near the PLP-Lys(45) Schiff base. A theoretical model of the enzyme-D-serine complex suggested that the hydroxyl group of D-serine directly coordinates the zinc ion, and that the ε-NH(2) group of Lys(45) is a short distance from the substrate Cα atom. The α-proton abstraction from D-serine by Lys(45) and the elimination of the hydroxyl group seem to occur with the assistance of the zinc ion, resulting in the strict reaction specificity.

PubMed: 21676877
DOI: 10.1074/jbc.M110.201160

Experimental method

X-RAY DIFFRACTION (2.09 Å)