Berezovsky IN

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

The Recipe for Protein-Based Function Predition and its implementation in the ANNOTATOR Software Environment

Published date : 27 Apr 2016

As biomolecular sequencing is becoming the main technique in life sciences, functional interpretation of sequences in terms of biomolecular mechanisms with in silico approaches is getting increasingly significant. Function prediction tools are most powerful for protein-coding sequences; yet, the concepts and technologies used for this purpose are not well reflected in bioinformatics textbooks. Notably, protein sequences typically consist of globular domains and non-globular segments. The two types of regions require cardinally different approaches for function prediction.

type
Book/Book Chapter
journal
Data Mining Techniques for the Life Sciences, Vol. 1415, pg 477-506,2016, ISBN: 978-1-4939-3570-3

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

Nucleotide binding database NBDB – a collection of sequence motifs with specific protein-ligand interactions

Published date : 26 Oct 2015

NBDB database describes proteinmotifs, elementary functional loops (EFLs) that are involved in binding

type
Journal Paper
journal
Nucleic Acids Research, 2015, doi: 10.1093/nar/gkv1124
Impact Factor
9.112

Organization of the multiaminoacyl-tRNA synthetase complex and the cotranslational protein folding

Published date : 30 Jun 2015

Aminoacyl-tRNA synthetases (ARSs) play an essential role in the protein synthesis by catalyzing an attachment of their cognate amino acids to tRNAs. Unlike their prokaryotic counterparts, ARSs in higher eukaryotes form a multiaminoacyl-tRNA synthetase complex (MARS), consisting of the subset of ARS polypeptides and three auxiliary proteins. The intriguing feature of MARS complex is the presence of only nine out of twenty ARSs, specific for Arg, Asp, Gln, Glu, Ile, Leu, Lys, Met, and Pro, regardless of the organism, cell, or tissue types.

type
Journal Paper
journal
Protein Science 24 (2015) Pg. 1475-1485, doi: 10.1002/pro.2735

Protein function from its emergence to diversity in contemporary proteins

Published date : 09 Jun 2015

The goal of this work is to learn from nature the rules that govern evolution and the design of protein function. The fundamental laws of physics lie in the foundation of the protein structure and all stages of the protein evolution, determining optimal sizes and shapes at different levels of structural hierarchy. We looked back into the very onset of the protein evolution with a goal to find elementary functions (EFs) that came from the prebiotic world and served as building blocks of the first enzymes.

type
Journal Paper
journal
Physical Biology, Vol. 12, No. 4, 2015, doi:10.1088/1478-3975/12/4/045002
Impact Factor
2.536

The fundamental tradeoff in genomes and proteomes of prokaryotes established by the genetic code, codon entropy, and physics of nucleic acids and proteins

Published date : 12 Dec 2014

Background: Mutations in nucleotide sequences provide a foundation for genetic variability, and selection is the driving force of the evolution and molecular adaptation. Despite considerable progress in the understanding of selective forces and their compositional determinants, the very nature of underlying mutational biases remains unclear.

type
Journal Paper
journal
Biology Direct 2014 Mar;42(5):2879-92. doi: 10.1093/nar/gkt1336
Impact Factor
4.04