L. Mario Amzel, Ph.D.
Dr. L. Mario Amzel is a Professor and director of the Biophysics and Biophysical Chemistry Department at the Johns Hopkins University School of Medicine.
Dr. Amzel’s research focuses on understanding how the structures of proteins drive their physiological function.
Methods such as cloning and expression, site-directed mutagenesis, x-ray diffraction, kinetics and thermodynamic measurements and computational techniques are all combined to provide information about the detailed mechanisms of several key biological systems. Insight gained from these studies lead to in-depth understanding not only of normal function but also of the possible effects of malfunctioning in disease situations. In most cases, drug design is a natural extension of these studies.
Structural Enzymology. Enzymes play a key role in all metabolic and cell-signaling processes. Characterization of an enzyme’s biological function must include the description of its mechanisms at an atomic level. Our laboratory is deciphering the catalytic mechanism of several enzyme families, using a combination of molecular biology, biochemistry and structural Biology. Systems under study fall into two classes: enzymes that recognize or process phosphates and redox enzymes. These systems include: pyrophosphate hydrolases, farnesyl pyrophosphate synthases, PI3K, flavoenzymes and copper hydroxylases. All experiments necessary to address mechanistic questions are carried out in the laboratory. Cloning and expression, ultrapurification, kinetic characterization, mutational analysis, mass spectrometry, crystallization, and structure determination by x-ray diffraction are some of the techniques we bring to bear to characterize the mechanisms of these enzymes. In addition to being intrinsically interesting some of these systems are being developed as targets for drug design.
Mechanism and regulation of channels and transporters. We are studying the regulation of the cardiac voltage regulated Na+ channel Nav 1.5 by calmodulin using structural and thermodynamic techniques.
A major project involves studying the structure and the mechanisms of the I– transport by the Na+ / I– symporter. We are using experimental and computational methods to identify the different molecular species that participate in the transport cycle.
Transporters and channels. Ion movements across biological membranes are highly specific processes at the core of numerous moving physiological conditions and disease states. We are studying the mechanism of the Na+ / I–symporter, NIS, and the control of the activity of voltage- activated Na+ channels by two key effectors – calmodulin and Ca2+.