BEREZOVSKY Igor

Simple yet functional phosphate-loop proteins

Published date : 30 Nov 2018

Abundant and essential motifs, such as phosphate-binding loops (P-loops), are presumed to be the seeds of modern enzymes. The Walker-A P-loop is absolutely essential in modern NTPase enzymes, in mediating binding, and transfer of the terminal phosphate groups of NTPs. However, NTPase function depends on many additional active-site residues placed throughout the protein’s scaffold. Can motifs such as P-loops confer function in a simpler context?

type
Journal Paper
journal
Proceedings of the National Academy of Sciences of the United States of America, PNAS, doi: 10.1073/pnas.1812400115
Impact Factor
9.504

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.

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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.

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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.

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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.

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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