The Macromolecular Structures Program of the IMBB is focused on questions
related to the protein-folding problem, protein engineering and the analysis of
complex biological mechanisms using structural information obtained by X-ray
crystallography. The research projects and related activities carried out in
this context are mostly multidisciplinary international collaborations, mainly
within the framework of the initiatives of the European Union in the area of
Biotechnology. The continuing analysis of the folding and stability of 4-alpha
helical bundle proteins has proved extremely useful in the understanding of
this recurrent tertiary motif, so that our results could help biotechnology to
advance in the area of protein design from a trial-and-error to a rational
protein-engineering mode. An extensive network of collaborations with other
IMBB groups has helped us to make significant progress towards an understanding
of the structural basis of three major types of protein-DNA interactions, i.e.,
those of endonucleases, DNA-methylases and zinc-fingers. Numerous
three-dimensional structures of peptaibols antibotics have been determined in
our laboratory; these could lead to the design of novel antibiotics with
improved properties. The elucidation of electron transfer mechanisms via
protein-protein interactions is the goal of the crystallographic and
spectroscopic analysis of copper containing proteins; the structures of several
oxidized and reduced states of pseudoazurin as well as the metal-free
apo-pseudoazurin have been determined. With the studies of the apolipoprotein
A-I and of HIV regulating proteins, our group has recently initiated projects
of considerable medical interest. European Union supports a new project which
starts in our lab concerning the design of TIM-barrel proteins. In particular,
structural analyses of thermostable and engineered chitinases as well as their
complexes with substrate analogues and inhibitors will be carried out aiming at
faster, smaller and more stable chitinase structures. An important aspect of
our activities has been the organization of several international training
courses and workshops. The main objective of these efforts is to help create at
the IMBB conditions favouring high-quality research and training in the
structural studies of biological macromolecules.
