bound (complex) form (if both are available). We previously
demonstrated that these maps identify allosteric response of the
protein structural networks [11, 20].
4 Applications
Herein, we present a short survey of possible applications of the
method, with reference to some of our previous works and relevant
literature in the field.
4.1 Allostery
in Protein-Ligand
Binding
The capital application of the method in allostery identification
deals with the identification of allosteric activation in protein-ligand
binding.
De Ruvo and coworkers highlighted a specific response in
allosteric proteins, not present in non-allosteric proteins undergoing binding, such as albumin [11]. The paper focused on
calcium-binding proteins, traditionally parted into sensors (allosteric) and buffers (non-allosteric). Starting on this well-defined classification, we reported projections of P onto protein sequence
(Fig. 5).
In this work, we highlighted a sharp change of P values in
regions close to the active site upon binding, while fainter changes
are appreciable in non-allosteric forms (see Fig. 5).
In more recent works, we reported maps of ΔP (see Note 4) for
different forms of a class of plant enzymes, which are in charge of
many different reactions in common plant organisms. We compared also ΔP maps (see Note 5) with corresponding displacement,
finding out an intriguing result: Fig. 6 reports results for cell
invertase from Arabidopsis Thaliana. First of all, clustering well
identifies functional domains (Fig. 6a). Then, upon binding,
P increases in the region between the two domains (Fig. 6b). One
may think it is only a result of a rigid displacement of the two
domains, but the displacement map (Fig. 6c) tells a different
story: only outer, more flexible regions move upon binding, while
the interdomain region remains practically motionless.
This case is particularly intriguing since this allosteric activation
does not result into a conformational change, falling in the category
of entropically driven allosteric transitions—of great interest since
only recently identified and classified [26].
4.2 Allostery
in Protein-Protein
Interactions
A very hot topic in the field of drug discovery is the identification of
allosteric sites to modulate protein-protein interactions [27]. In
this perspective, the allosteric drugs analysis strongly relies on the
network paradigm [28].
In 2015, we presented a work focused on the analysis of the
anthrax complexes [29]: it is a trimeric complex made up of a
protective agent (PA), an edema factor (EF), and a lethal factor
16
Luisa Di Paola et al.
demonstrated that these maps identify allosteric response of the
protein structural networks [11, 20].
4 Applications
Herein, we present a short survey of possible applications of the
method, with reference to some of our previous works and relevant
literature in the field.
4.1 Allostery
in Protein-Ligand
Binding
The capital application of the method in allostery identification
deals with the identification of allosteric activation in protein-ligand
binding.
De Ruvo and coworkers highlighted a specific response in
allosteric proteins, not present in non-allosteric proteins undergoing binding, such as albumin [11]. The paper focused on
calcium-binding proteins, traditionally parted into sensors (allosteric) and buffers (non-allosteric). Starting on this well-defined classification, we reported projections of P onto protein sequence
(Fig. 5).
In this work, we highlighted a sharp change of P values in
regions close to the active site upon binding, while fainter changes
are appreciable in non-allosteric forms (see Fig. 5).
In more recent works, we reported maps of ΔP (see Note 4) for
different forms of a class of plant enzymes, which are in charge of
many different reactions in common plant organisms. We compared also ΔP maps (see Note 5) with corresponding displacement,
finding out an intriguing result: Fig. 6 reports results for cell
invertase from Arabidopsis Thaliana. First of all, clustering well
identifies functional domains (Fig. 6a). Then, upon binding,
P increases in the region between the two domains (Fig. 6b). One
may think it is only a result of a rigid displacement of the two
domains, but the displacement map (Fig. 6c) tells a different
story: only outer, more flexible regions move upon binding, while
the interdomain region remains practically motionless.
This case is particularly intriguing since this allosteric activation
does not result into a conformational change, falling in the category
of entropically driven allosteric transitions—of great interest since
only recently identified and classified [26].
4.2 Allostery
in Protein-Protein
Interactions
A very hot topic in the field of drug discovery is the identification of
allosteric sites to modulate protein-protein interactions [27]. In
this perspective, the allosteric drugs analysis strongly relies on the
network paradigm [28].
In 2015, we presented a work focused on the analysis of the
anthrax complexes [29]: it is a trimeric complex made up of a
protective agent (PA), an edema factor (EF), and a lethal factor
16
Luisa Di Paola et al.