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PDBsum entry 3l6c
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References listed in PDB file
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Key reference
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Title
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The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding.
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Authors
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M.A.Smith,
V.Mack,
A.Ebneth,
I.Moraes,
B.Felicetti,
M.Wood,
D.Schonfeld,
O.Mather,
A.Cesura,
J.Barker.
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Ref.
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J Biol Chem, 2010,
285,
12873-12881.
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PubMed id
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Abstract
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Serine racemase is responsible for the synthesis of D-serine, an endogenous
co-agonist for N-methyl-D-aspartate receptor-type glutamate receptors (NMDARs).
This pyridoxal 5'-phosphate-dependent enzyme is involved both in the reversible
conversion of L- to D-serine and serine catabolism by alpha,beta-elimination of
water, thereby regulating D-serine levels. Because D-serine affects NMDAR
signaling throughout the brain, serine racemase is a promising target for the
treatment of disorders related to NMDAR dysfunction. To provide a molecular
basis for rational drug design the x-ray crystal structures of human and rat
serine racemase were determined at 1.5- and 2.1-A resolution, respectively, and
in the presence and absence of the orthosteric inhibitor malonate. The
structures revealed a fold typical of beta-family pyridoxal 5'-phosphate
enzymes, with both a large domain and a flexible small domain associated into a
symmetric dimer, and indicated a ligand-induced rearrangement of the small
domain that organizes the active site for specific turnover of the substrate.
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