2ZR8
Crystal Structure of Modified Serine Racemase complexed with Serine
Summary for 2ZR8
| Entry DOI | 10.2210/pdb2zr8/pdb |
| Descriptor | Uncharacterized protein C320.14, N-(5'-PHOSPHOPYRIDOXYL)-D-ALANINE, SERINE, ... (5 entities in total) |
| Functional Keywords | plp-dependent, lyase, pyridoxal phosphate, isomerase |
| Biological source | Schizosaccharomyces pombe (Fission yeast) |
| Total number of polymer chains | 1 |
| Total formula weight | 35542.82 |
| Authors | Goto, M. (deposition date: 2008-08-25, release date: 2009-07-28, Last modification date: 2024-11-20) |
| Primary citation | Goto, M.,Yamauchi, T.,Kamiya, N.,Miyahara, I.,Yoshimura, T.,Mihara, H.,Kurihara, T.,Hirotsu, K.,Esaki, N. Crystal structure of a homolog of mammalian serine racemase from Schizosaccharomyces pombe J.Biol.Chem., 284:25944-25952, 2009 Cited by PubMed Abstract: D-serine is an endogenous coagonist for the N-methyl-D-aspartate receptor and is involved in excitatory neurotransmission in the brain. Mammalian pyridoxal 5'-phosphate-dependent serine racemase, which is localized in the mammalian brain, catalyzes the racemization of L-serine to yield D-serine and vice versa. The enzyme also catalyzes the dehydration of D- and L-serine. Both reactions are enhanced by Mg.ATP in vivo. We have determined the structures of the following three forms of the mammalian enzyme homolog from Schizosaccharomyces pombe: the wild-type enzyme, the wild-type enzyme in the complex with an ATP analog, and the modified enzyme in the complex with serine at 1.7, 1.9, and 2.2 A resolution, respectively. On binding of the substrate, the small domain rotates toward the large domain to close the active site. The ATP binding site was identified at the domain and the subunit interface. Computer graphics models of the wild-type enzyme complexed with L-serine and D-serine provided an insight into the catalytic mechanisms of both reactions. Lys-57 and Ser-82 located on the protein and solvent sides, respectively, with respect to the cofactor plane, are acid-base catalysts that shuttle protons to the substrate. The modified enzyme, which has a unique "lysino-D-alanyl" residue at the active site, also exhibits catalytic activities. The crystal-soaking experiment showed that the substrate serine was actually trapped in the active site of the modified enzyme, suggesting that the lysino-D-alanyl residue acts as a catalytic base in the same manner as inherent Lys-57 of the wild-type enzyme. PubMed: 19640845DOI: 10.1074/jbc.M109.010470 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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