Sergey Korolev, PhD

Bio

Korolev SergeyIn 1993, I received my PhD in molecular biology from the Russian Academy of Science in Moscow. I am now an associate professor of biochemistry and molecular. biology at Saint Louis University School of Medicine. My research interests include structural studies of certain proteins and enzymes involved in genome maintenance, ovarian cancer development, breast cancer metastasis and other cancers. I am also passionate about collaborating with experts in other fields on research projects.

Research

My laboratory investigates structure and mechanism of pro- and eukaryotic DNA repair proteins and recombination mediator proteins (RMPs) to understand basic principles of nucleic acids metabolism and to advance novel therapy. Newly discovered structural features and mechanistic properties are targeted for drug design using computational and high throughput screening methods. Analysis of proteins from different kingdoms of life lead to discoveries of new fundamental mechanisms. Our studies of bacterial RMPs lead to discovery of novel properties of human tumor suppressor PALB2 (Partner and Localizer of BRCA2) which include localization and characterization DNA-binding motif and its critical role for cellular DNA repair. Surprisingly, we discovered that PALB2 not only stimulate DNA recombination by a major recombinase RAD51, but supports strand-exchange reaction by itself. This finding is particularly significant since PALB2 is only the third known protein with such activity, in addition to major recombinase RecA/RAD51 and recombination mediator RAD52. Moreover, its structure is predicted to be completely different from those proteins. We collaborate with experts throughout biochemical screening, in silico screening and medicinal chemistry to identify lead candidates for inhibition of two key interactions of PALB2 which affect fitness of cancer cells and their response to chemotherapy.

We collaborate with other research groups, providing our expertise in structural biology. One such collaborative project includes LINE-1 human retrotransposone implicated in aging and cancer. We revealed a unique mechanism of conformation-based sequence recognition and catalysis advantageous for specific role of L1EN in providing polyT DNA primer for initiation of reverse transcription reaction and propagating LINE1 throughout genome.

Recent publications

Redington J, Deveryshetty J, Kanikkannan L, Miller I, Korolev S. Structural Insight into the Mechanism of PALB2 Interaction with MRG15. Genes (Basel). 2021 Dec 17;12(12):2002.

Miller I, Totrov M, Korotchkina L, Kazyulkin DN, Gudkov AV, Korolev S. Structural dissection of sequence recognition and catalytic mechanism of human LINE-1 endonuclease. Nucleic Acids Res. 2021 Sep 23.

Deveryshetty J, Peterlini T, Ryzhikov M, Brahiti N, Dellaire G, Masson JY, Korolev S. Novel RNA and DNA strand exchange activity of the PALB2 DNA binding domain and its critical role for DNA repair in cells. Elife. 2019.

Lu X, Malley KR, Brenner CC, Koroleva O, Korolev S*, Downes BP. A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes. Nature Commun. 2016, 7:12580. (*co-corresponding author).

Malley KR, Koroleva O, Miller I, Sanishvili R, Jenkins CM, Gross RW, Korolev S. The structure of iPLA2β reveals dimeric active sites and suggests mechanisms of regulation and localization. Nature Commun. 2018; 9(1):765.

Korolev. S, Advances in Structural Studies of Recombination Mediator Proteins. Biophys. Chem. 2017, 225:27-37.

Ryzhikov M, Postnov D, Koroleva O, Tran, A, Korolev S. Mechanism of RecO recruitment to DNA by single-stranded DNA binding protein. Nucleic Acids Res. 2011; 39(14):6305-14.