title: Structure and substrate recognition of the Staphylococcus aureus protein tyrosine phosphatase PtpA.
abstract: Phosphosignaling through pSer/pThr/pTyr is emerging as a common signaling mechanism in prokaryotes. The human pathogen Staphylococcus aureus produces two low-molecular-weight protein tyrosine phosphatases (PTPs), PtpA and PtpB, with unknown functions. To provide the structural context for understanding PtpA function and substrate recognition, establish PtpA's structural relations within the PTP family, and provide a framework for the design of specific inhibitors, we solved the crystal structure of PtpA at 1 Å resolution. While PtpA adopts the common, conserved PTP fold and shows close overall similarity to eukaryotic PTPs, several features in the active site and surface organization are unique and can be explored to design selective inhibitors. A peptide bound in the active site mimics a phosphotyrosine substrate, affords insight into substrate recognition, and provides a testable substrate prediction. Genetic deletion of ptpA or ptpB does not affect in vitro growth or cell wall integrity, raising the possibility that PtpA and PtpB have specialized functions during infection.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Vega
authors.forename: Seemay
authors.initials: S
authors.lastname: Chou
authors.forename: Katherine
authors.initials: K
authors.lastname: Engel
authors.forename: Maria E
authors.initials: ME
authors.lastname: Harrell
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rajagopal
authors.forename: Christoph
authors.initials: C
authors.lastname: Grundner
mesh_terms: D020134:Catalytic Domain; D002473:Cell Wall / Q000502:physiology; D018360:Crystallography, X-Ray; D017353:Gene Deletion; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D017027:Protein Tyrosine Phosphatases