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Advances in Structure, Function and Molecular Targeting of DNA Topoisomerases...
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Advances in Structure, Function and Molecular Targeting of DNA Topoisomerases 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 September 2024 | Viewed by 528

Special Issue Editors

Prof. Dr. Joseph E. Deweese

E-Mail Website
Guest Editor
1. Professor of Biochemistry, Freed-Hardeman University, Henderson, TN 38340, USA
2. Adjunct Associate Professor, Biochemistry Department, Vanderbilt University, Nashville, TN 37232, USA
Interests: DNA topoisomerases
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Neil Osheroff

E-Mail Website
Guest Editor
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Interests: topoisomerase
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Topoisomerases are essential enzymes in living systems that play critical roles in transcription, replication, cell division, and DNA damage repair. Over the last 45+ years, many facets of the function of these enzymes have been elucidated, but critical questions remain. Although attempts to answer some fundamental questions of functions and mechanisms have been made, additional questions related to regulation, localization, and protein–protein interactions have been raised. Further, the utility of anticancer and antibacterial drugs targeting topoisomerases has been widely recognized, and many chemotherapeutic regimens still include topoisomerase poisons. Thus, we must continue to explore both the available agents and new ones.

This Special Issue of the International Journal of Molecular Sciences focuses on topoisomerases and welcomes both original research articles and review papers that deal with advances in our understanding of topoisomerase structures, functions, and molecular targeting for therapeutic purposes.

Prof. Dr. Joseph E. Deweese
Prof. Dr. Neil Osheroff
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • topoisomerase
  • DNA supercoiling
  • DNA topology
  • anticancer
  • antimicrobial
  • DNA damage

Published Papers (1 paper)

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Research

19 pages, 4292 KiB  
Article
Bioinformatic Analysis of Topoisomerase IIα Reveals Interdomain Interdependencies and Critical C-Terminal Domain Residues
by Clark E. Endsley, Kori A. Moore, Thomas D. Townsley, Kirk K. Durston and Joseph E. Deweese
Int. J. Mol. Sci. 2024, 25(11), 5674; https://doi.org/10.3390/ijms25115674 - 23 May 2024
Viewed by 236
Abstract
DNA Topoisomerase IIα (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential [...] Read more.
DNA Topoisomerase IIα (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis, including the PSICalc algorithm, Shannon entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of the third, fourth, and fifth order, including positions that had been previously analyzed via mutation and biochemical assays, were identified. Some of these clusters coincided with positions that, when mutated, either increased or decreased relaxation activity. Finally, sites of low Shannon entropy (i.e., low variation in amino acids at a given site) were identified and mapped as key positions in the CTD. Included in the low-entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis. Full article
(This article belongs to the Special Issue Advances in Structure, Function and Molecular Targeting of DNA Topoisomerases 2.0)
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