ABSTRACT
Proteins can use aromatic side-chains to stabilize bound cationic ligands through cation-pi interactions. Here, we report the first example of the reciprocal process, termed pi-cation, in which a cationic protein side-chain stabilizes a neutral aromatic ligand. Site-directed mutagenesis revealed that an arginine side-chain located in the deep binding pocket of a monoclonal antibody (4D5) is essential for binding the neutral polynuclear aromatic hydrocarbon benzo[a]pyrene. This Arg was very likely selected for in the primary response, further underscoring the importance of the pi-cation interaction for ligand binding, which should be considered in protein analysis and design when ligands include aromatic groups.
Subject(s)
Benzo(a)pyrene/chemistry , Benzo(a)pyrene/metabolism , Binding Sites, Antibody , Cations/chemistry , Cations/metabolism , Immunoglobulin Variable Region/chemistry , Amino Acid Sequence , Amino Acid Substitution/genetics , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/immunology , Antigen-Antibody Complex/chemistry , Antigen-Antibody Complex/genetics , Antigen-Antibody Complex/immunology , Arginine/genetics , Arginine/metabolism , Base Sequence , Binding Sites, Antibody/genetics , Binding Sites, Antibody/immunology , Enzyme-Linked Immunosorbent Assay , Haptens/chemistry , Haptens/immunology , Haptens/metabolism , Immunoglobulin Variable Region/genetics , Immunoglobulin Variable Region/immunology , Ligands , Lysine/genetics , Lysine/metabolism , Mice , Models, Molecular , Mutagenesis, Site-Directed/genetics , Mutation/genetics , Static Electricity , ThermodynamicsSubject(s)
Delivery of Health Care, Integrated/statistics & numerical data , Information Systems/statistics & numerical data , Data Collection , Decision Making, Organizational , Information Systems/economics , Investments/economics , Investments/standards , Personnel Turnover , Quality of Health Care , Systems Integration , United StatesSubject(s)
Blue Cross Blue Shield Insurance Plans/organization & administration , Consumer Advocacy/legislation & jurisprudence , Blue Cross Blue Shield Insurance Plans/legislation & jurisprudence , California , Community Participation , Foundations/organization & administration , Humans , New York , Organizational Innovation , Organizations, Nonprofit/legislation & jurisprudence , United StatesSubject(s)
Hospital-Patient Relations , Patient Satisfaction , Patient-Centered Care , Humans , United StatesABSTRACT
This special section marks the 20th anniversary of Crain Communications' ownership of Modern Healthcare. On the following pages, the staff of Modern Healthcare examines the three most important developments of the past two decades (p. 44) and then reviews in detail the news events, trends and people that shaped each year (pages 46-84). A compilation of some of the best work of editorial cartoonist Roger Schillerstrom can be found on p. 86. Finally, with the help of healthcare futurists, we'll take a peek at the next 20 years of healthcare (pages 92-96) as this most changeable of industries undergoes ever more profound transformations.
Subject(s)
Anniversaries and Special Events , Delivery of Health Care/trends , Periodicals as Topic , Delivery of Health Care/legislation & jurisprudence , Forecasting , Health Policy/legislation & jurisprudence , Health Policy/trends , United StatesSubject(s)
Delivery of Health Care , Public Opinion , Communication , Dictionaries as Topic , Humans , Terminology as TopicSubject(s)
Consumer Advocacy , Health Services Accessibility , Female , Financing, Organized , Foundations , Humans , Maternal Health Services , United StatesABSTRACT
The cDNAs from a hybridoma (mAb 481.1) specific for diuron, a widely used phenylurea herbicide, were cloned into the phage display vector pComb8. Antigen-binding clones were selected by panning on diuron-hapten-BSA conjugates. The nucleotide and deduced amino-acid sequences encoding the Fab regions of the light (kappa) and heavy (gamma) chains were determined. The light chain was from mouse kappa chain subgroup III and the heavy chain was a member of the mouse H chain subgroup III(d).