Guarnera Enrico

On the perturbation nature of allostery: sites, mutations, and signal modulation

Published date : 12 Nov 2018

Regardless of the diversity of systems, allosteic signalling is found to be always caused by perturbations. This recurring trait of allostery serves as a foundation for developing different experimental efforts and theoretical models for the studies of allosteric mechanisms. Among computational approaches considered here particular emphasis is given to the structure-based statistical mechanical model of allostery (SBSMMA), which allows one to study the causality and energetics of allosteric communication.

type
Journal Paper
journal
Current Opinion in Structural Biology, Vol. 56, June 2019, Pg 18-27, doi: 10.1016/j.sbi.2018.10.008
Impact Factor
7.179

AlloMAPS: allosteric mutation analysis and polymorphism of signaling database

Published date : 26 Oct 2018

AlloMAPS database provides data on the causality and energetics of allosteric communication obtained with the structure-based statistical mechanical model of allostery (SBSMMA). The database contains data on allosteric signaling in three sets of proteins and protein chains: (i) 46 proteins with comprehensively annotated functional and allosteric sites; (ii) 1908 protein chains from PDBselect set of chains with low (<25%) sequence identity; (iii) 33 proteins with more than 50 known pathological SNPs in each molecule.

type
Journal Paper
journal
Nucleic Acis Research, 2018, Oct 26, doi:10.1093/nar/gky1028
Impact Factor
11.561

Reversing allosteric communication: From detecting allosteric sites to inducing and tuning targeted allosteric response

Published date : 18 Jun 2018

The omnipresence of allosteric regulation together with the fundamental role of structural dynamics in this phenomenon have initiated a great interest to the detection of regulatory exosites and design of corresponding effectors.

type
Journal Paper
journal
PLoS Computational Biology, 18 Jun 2018, doi:10.1371/journal.pcbi.1006228
Impact Factor
3.955

Insulin-Degrading Enzyme in the Fight against Alzheimer's Disease

Published date : 29 Nov 2017

After decades of research and clinical trials there is still no cure for Alzheimer's disease (AD). While impaired clearance of amyloid beta (Aβ) peptides is considered as one of the major causes of AD, it was recently complemented by a potential role of other toxic amyloidogenic species. Insulin-degrading enzyme (IDE) is the proteolytic culprit of various β-forming peptides, both extracellular and intracellular.

type
Journal Paper
journal
Trends in Pharmacological Sciences, 10 Nov 2017, doi : 10.1016/j.tips.2017.10.008
Impact Factor
12.797

AlloSigMA: Allosteric Signalling and Mutation Analysis server

Published date : 06 Jul 2017

Motivation: Allostery is an omnipresent mechanism of the function modulation in proteins via either effector binding or mutations in the exosites. Despite the growing number of on-line servers and databases devoted to prediction/classification of allosteric sites and their characteristics, there is a lack of resources for an efficient and quick estimation of the causality and energetics of allosteric communication.

type
Journal Paper
journal
Bioinformatics, 2017, doi: 10.1093/bioinformatics/btx430
Impact Factor
7.307

Towards allosterically increased catalytic activity of insulin degrading enzyme (IDE) against amyloid peptides

Published date : 03 Dec 2016

Physiological role of insulin degrading enzyme (IDE) in the intracytosolic clearance of amyloid beta (Aβ) and other amyloid-like peptides supports a hypothesis that human IDE hyperactivation could be therapeutically beneficial in the treatment of the late onset Alzhimer’s disease (AD). The major challenge towards this goal is to increase specific catalytic activity of IDE against the Aβ-substrate.

type
Journal Paper
journal
Biochemistry 2016, doi: 10.1021/acs.biochem.6b00783
Impact Factor
2.87

Protein function machinery: from basic structural units to modulation of activity

Published date : 16 Nov 2016

Contemporary protein structure is a result of the trade off between the laws of physics and the evolutionary selection. The polymer nature of proteins played a decisive role in establishing the basic structural and functional units of soluble proteins. We discuss how these elementary building blocks work in the hierarchy of protein domain structure, co-translational folding, as well as in enzymatic activity and molecular interactions.

type
Journal Paper
journal
Current Opinion in Structural Biology, Vol. 42, Feb 17, Pg 67-74, doi: 10.1016/j.sbi.2016.10.021
Impact Factor
6.7

Basic units of protein structure, folding, and function

Published date : 30 Sep 2016

Study of the hierarchy of domain structure with alternative sets of domains and analysis of discontinuous domains, consisting of remote segments of the polypeptide chain, raised a question about the minimal structural unit of the protein domain. The hypothesis on the decisive role of the polypeptide backbone in determining the elementary units of globular proteins have led to the discovery of closed loops.

type
Journal Paper
journal
Progress in Biophysics and Molecular Biology, 2016, Sep 30, doi: 10.1016/j.pbiomolbio.2016.09.009
Impact Factor
2.58

Structure-Based Statistical Mechanical Model Accounts for the Causality and Energetics of Allosteric Communication

Published date : 03 Mar 2016

Allostery is one of the pervasive mechanisms through which proteins in living systems carry out enzymatic activity, cell signaling, and metabolism control. Effective modeling of the protein function regulation requires a synthesis of the thermodynamic and structural views of allostery.We present here a structure-based statistical mechanical model of allostery, allowing one to observe causality of communication between regulatory and functional sites, and to estimate per residue free energy changes.

type
Journal Paper
journal
PLOS Computational Biology, 2016, doi:10.1371/journal.pcbi.1004678
Impact Factor
4.62

Allosteric sites: remote control in regulation of protein activity

Published date : 09 Nov 2015

The presence of multiple allosteric sites in proteins motivates development of allosteric drugs — modulators of protein activity with potentially higher specificity and less toxicity than traditional orthosteric compounds. A quest for allosteric control of any protein starts from the identification and characterization of allosteric sites. Protein dynamics is the basis for allosteric communication. Binding of effector molecules to allosteric sites modulates structural dynamics, thus affecting activity of

type
Journal Paper
journal
Current Opinion in Structural Biology, 9 Nov 2015, Vol. 37, Pg 1-8, doi: 10.1016/j.sbi.2015.10.004
Impact Factor
7.2