5X2L

Crystal Structure of Human Serine Racemase

Summary for 5X2L

• Entry DOI: 10.2210/pdb5x2l/pdb
• Descriptor: Serine racemase, PYRIDOXAL-5'-PHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: serine racemase, pyridoxal-5'-phosphate, human, lyase, isomerase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 75891.38

Authors

Obita, T.,Matsumoto, K.,Mori, H.,Toyooka, N.,Mizuguchi, M. (deposition date: 2017-02-01, release date: 2018-01-31, Last modification date: 2025-04-09)

Primary citation

Takahara, S.,Nakagawa, K.,Uchiyama, T.,Yoshida, T.,Matsumoto, K.,Kawasumi, Y.,Mizuguchi, M.,Obita, T.,Watanabe, Y.,Hayakawa, D.,Gouda, H.,Mori, H.,Toyooka, N.
Design, synthesis, and evaluation of novel inhibitors for wild-type human serine racemase.
Bioorg. Med. Chem. Lett., 2017

PubMed Abstract: Most of the endogenous free d-serine (about 90%) in the brain is produced by serine racemase (SR). d-Serine in the brain is involved in neurodegenerative disorders and epileptic states as an endogenous co-agonist of the NMDA-type glutamate receptor. Thus, SR inhibitors are expected to be novel therapeutic candidates for the treatment of these disorders. In this study, we solved the crystal structure of wild-type SR, and tried to identify a new inhibitor of SR by in silico screening using the structural information. As a result, we identified two hit compounds by their in vitro evaluations using wild-type SR. Based on the structure of the more potent hit compound 1, we synthesized 15 derivatives and evaluated their inhibitory activities against wild-type SR. Among them, the compound 9C showed relatively high inhibitory potency for wild-type SR. Compound 9C was a more potent inhibitor than compound 24, which was synthesized by our group based upon the structural information of the mutant-type SR.

PubMed: 29277459
DOI: 10.1016/j.bmcl.2017.12.021

Experimental method

X-RAY DIFFRACTION (1.806 Å)