Identification of a novel ligand binding site in phosphoserine phosphatase from the hyperthermophilic archaeon Thermococcus onnurineus

Cited 5 time in scopus
Metadata Downloads

Full metadata record

DC FieldValueLanguage
dc.contributor.authorTae Yang Jung-
dc.contributor.authorY S Kim-
dc.contributor.authorB H Oh-
dc.contributor.authorEuijeon Woo-
dc.description.abstractPhosphoserine 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 A 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 kcat/KM 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.-
dc.titleIdentification of a novel ligand binding site in phosphoserine phosphatase from the hyperthermophilic archaeon Thermococcus onnurineus-
dc.title.alternativeIdentification of a novel ligand binding site in phosphoserine phosphatase from the hyperthermophilic archaeon Thermococcus onnurineus-
dc.citation.titleProteins-Structure Function and Bioinformatics-
dc.contributor.affiliatedAuthorTae Yang Jung-
dc.contributor.affiliatedAuthorEuijeon Woo-
dc.identifier.bibliographicCitationProteins-Structure Function and Bioinformatics, vol. 81, no. 5, pp. 819-829-
dc.subject.keywordCAP module-
dc.subject.keywordHAD family-
dc.subject.keywordLigand binding-
dc.subject.keywordPhosphoserine phosphatase-
dc.subject.localCAP module-
dc.subject.localHAD family-
dc.subject.localLigand binding-
dc.subject.localPhosphoserine phosphatase-
dc.subject.localphosphoserine phosphatase-
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.

Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.