title: Atomic resolution crystal structure of VcLMWPTP-1 from Vibrio cholerae O395: insights into a novel mode of dimerization in the low molecular weight protein tyrosine phosphatase family.
abstract: Low molecular weight protein tyrosine phosphatase (LMWPTP) is a group of phosphotyrosine phosphatase ubiquitously found in a wide range of organisms ranging from bacteria to mammals. Dimerization in the LMWPTP family has been reported earlier which follows a common mechanism involving active site residues leading to an enzymatically inactive species. Here we report a novel form of dimerization in a LMWPTP from Vibrio cholera 0395 (VcLMWPTP-1). Studies in solution reveal the existence of the dimer in solution while kinetic study depicts the active form of the enzyme. This indicates that the mode of dimerization in VcLMWPTP-1 is different from others where active site residues are not involved in the process. A high resolution (1.45Å) crystal structure of VcLMWPTP-1 confirms a different mode of dimerization where the active site is catalytically accessible as evident by a tightly bound substrate mimicking ligand, MOPS at the active site pocket. Although being a member of a prokaryotic protein family, VcLMWPTP-1 structure resembles very closely to LMWPTP from a eukaryote, Entamoeba histolytica. It also delineates the diverse surface properties around the active site of the enzyme.
authors.affiliation: Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Nath
authors.affiliation: Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, India.
authors.forename: Ramanuj
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, India. Electronic address: udayaditya.sen@saha.ac.in.
authors.forename: Udayaditya
authors.initials: U
authors.lastname: Sen
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D019281:Dimerization; D008956:Models, Chemical; D008958:Models, Molecular; D008970:Molecular Weight; D011485:Protein Binding; D011487:Protein Conformation; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000145:classification / Q000648:ultrastructure*; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D017027:Protein Tyrosine Phosphatases
keywords: Active dimer; Bacterial protein phosphatases; Low molecular weight protein tyrosine phosphatases; X-ray crystallography