4AP9

Crystal structure of phosphoserine phosphatase from T. onnurineus in complex with NDSB-201

4AP9 の概要

• エントリーDOI: 10.2210/pdb4ap9/pdb
• 関連するPDBエントリー: 4B6J
• 分子名称: PHOSPHOSERINE PHOSPHATASE, 3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE (3 entities in total)
• 機能のキーワード: hydrolase, haloacid dehalogenase superfamily, ndsb
• 由来する生物種: THERMOCOCCUS ONNURINEUS
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94595.09

構造登録者

Jung, T.-Y.,Kim, Y.-S.,Song, H.-N.,Woo, E. (登録日: 2012-03-31, 公開日: 2012-12-26, 最終更新日: 2024-11-20)

主引用文献

Jung, T.-Y.,S-Kim, Y.,Oh, B.H.,Woo, E.
Identification of a Novel Ligand Binding Site in Phosphoserine Phosphatase from the Hyperthermophilic Archaeon Thermococcus Onnurineus.
Proteins, 81:819-, 2013

PubMed Abstract: Phosphoserine phosphatase (PSP) catalyzes the final and irreversible step of L-serine synthesis by hydrolyzing phosphoserine to produce L-serine and inorganic phosphate. Developing a therapeutic drug that interferes with serine production is of great interest to regulate the pathogenicity of some bacteria and control D-serine levels in neurological diseases. We determined the crystal structure of PSP from the hyperthermophilic archaeon Thermococcus onnurineus at 1.8 Å resolution, revealing an NDSB ligand bound to a novel site that is located in a fissure between the catalytic domain and the CAP module. The structure shows a half-open conformation of the CAP 1 module with a unique protruding loop of residues 150-155 that possesses a helical conformation in other structures of homologous PSPs. Activity assays indicate that the enzyme exhibits marginal PSP activity at low temperature but a sharp increase in the k(cat)/K(M) value, approximately 22 fold, when the temperature is increased. Structural and biochemical analyses suggest that the protruding loop in the active site might be an essential component for the regulation of the activity of PSP from hyperthermophilic T. onnurineus. Identification of this novel binding site distantly located from the catalytic site may be exploited for the development of effective therapeutic allosteric inhibitors against PSP activity.

PubMed: 23239422
DOI: 10.1002/PROT.24238

実験手法

X-RAY DIFFRACTION (1.783 Å)