Institute of Crystallography - CNR

Structural and mechanistic enzymology

Mechanistic enzymology of pharmacological targets by means of crystallographic, computational and kinetic techniques

Roughly one third of the marketed drugs act via the modulation of target enzymes activity. The development of enzyme inhibitors as new drug candidates require the accurate understanding of both the structural and the kinetic properties of the target enzyme. By combining protein crystallography, the use of computational methods for the simulation of protein-ligand docking and the kinetic modeling of enzyme activity/inhibition by the global fitting of full reaction time courses, a deep and accurate understanding of the protein-ligand interaction can be achieved, that is of utmost importance for the design of new drugs.
In our group expertise has been gained in the field of cholinestarses inhibitors as anti-Alzheimer’s therapeutics, and of inhibitors of the bacterial NAD biosynthesis as antibiotic agents.

Reference works

– Caliandro R, Pesaresi A, Cariati L, Procopio A, Oliverio M, Lamba D. Kinetic and structural studies on the interactions of Torpedo californica acetylcholinesterase with two donepezil-like rigid analogues. J Enzyme Inhib Med Chem. 2018 Dec;33(1):794-803. doi: 10.1080/14756366.2018.1458030.
– Zha X, Lamba D, Zhang L, Lou Y, Xu C, Kang D, Chen L, Xu Y, Zhang L, De Simone A, Samez S, Pesaresi A, Stojan J, Lopez MG, Egea J, Andrisano V, Bartolini M. Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography. J Med Chem. 2016 Jan 14;59(1):114-31. doi: 10.1021/acs.jmedchem.5b01119.