Structural Enzymology and Thermodynamics Group

Department of Biophysics and Biophysical Chemistry
Johns Hopkins University School of Medicine
Baltimore, Maryland 21205 USA



Dr. L. Mario Amzel  
Professor and Director  
Contact Info. Phone: (410) 955-3955
  FAX: (410) 955-0637
Tammy Watson


(410) 614-3279 


PDB Structures: deposited coordinates
(Select RECALL RESULTS for listing)

 Dr. L. Mario Amzel


Structural Mechanistic Biochemistry
. 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: 1) Enzymes that recognize or process phosphates and 2) redox enzymes. These systems include: pyrophosphate hydrolases (Nudix enzymes), farnesyl pyrophosphate synthases, phosphoinositide-3-kinases, flavoenzymes, copper hydroxylases, and non-heme iron diooxygenases. 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 and quantum mechanical calculations 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. 

Structural Thermodynamics. Binding and recognition are basic aspects of most biological processes. Most biological processes rely upon recognition and binding among macromolecules. We have developed several systems, such as anti-peptide antibodies and lectins, that we are using to study protein-ligand interactions. As part of this research, we are developing computational methods to calculate the changes in the thermodynamic variables (ΔG, ΔH, ΔS) that take place when a protein recognized another macromolecule or a small ligand. Techniques used in this work involve monoclonal antibody development, x-ray diffraction and calorimetry, followed by empirical parameterization, and molecular mechanics/dynamics and statistical mechanics calculations. Results of these studies have a major impact on our understanding of binding energetics, including the estimation of binding affinities for structure-based drug design.




Amzel Laboratory Johns Hopkins University School of Medicine