title: Investigating the impact of Asp181 point mutations on interactions between PTP1B and phosphotyrosine substrate.
abstract: Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and leptin signaling, which suggests that it is an attractive therapeutic target in type II diabetes and obesity. The aim of this research is to explore residues which interact with phosphotyrosine substrate can be affected by D181 point mutations and lead to increased substrate binding. To achieve this goal, molecular dynamics simulations were performed on wild type (WT) and two mutated PTP1B/substrate complexes. The cross-correlation and principal component analyses show that point mutations can affect the motions of some residues in the active site of PTP1B. Moreover, the hydrogen bond and energy decomposition analyses indicate that apart from residue 181, point mutations have influence on the interactions of substrate with several residues in the active site of PTP1B.
authors.affiliation: State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.
authors.forename: Lushan
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhao
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D006801:Humans; D006860:Hydrogen Bonding; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D019000:Phosphotyrosine / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D007328:Insulin; D020738:Leptin; D019000:Phosphotyrosine; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1