Experimental and Theoretical Approaches to Protein-Targeting Drug Discovery II

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: 29 November 2024 | Viewed by 1380

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Istituto di Biostrutture e Bioimmagini IBB-CNR, Via Tommaso De Amicis 95, 80145 Naples, Italy
Interests: pharmaceutical chemistry; neurodrugs; protein interactions; spectroscopy; computational chemistry; phytochemistry
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Dear Colleagues,

Following a very successful first run, we are pleased to announce the launch of a second edition of the Special Issue “Experimental and Theoretical Approaches to Protein-Targeting Drug Discovery”.

Protein-driven biological processes are of fundamental importance in biomedicine because they are related to pathologies of enormous social relevance, including cancer, neurodegeneration, and viral diseases, such as the recent COVID-19 pandemic. In this Special Issue, we wish to focus on the novel experimental and theoretical approaches for drug discovery, design, and development, with particular attention being paid to the mechanisms of drug interference with protein-driven biological pathways. Contributions on nucleic acid–protein interaction, aptamers, peptide aggregation, nucleopeptide chemistry, and antimicrobial polyamino acids are also welcome as they could improve our overall knowledge of the amino-acid-based biochemistry at the interface between drug design and therapy. Other themes of interest are inherent to computational chemistry, in particular, tp molecular docking and molecular dynamics, applied to protein and peptide science.

This Special Issue is open to the submission of both original articles and reviews that describe research and ideas on the themes outlined here for protein-based molecular strategies.

Dr. Caterina Vicidomini
Dr. Giovanni N. Roviello
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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • proteins
  • peptides
  • amyloid
  • aptamers
  • molecular docking
  • Alzheimer disease
  • Parkinson’s disease
  • neurodrugs
  • biotechnological enzymes
  • antiviral drugs
  • vaccines
  • biomolecular targets
  • COVID-19
  • SARS-CoV-2
  • spike protein
  • peptide aggregation
  • drug repurposing
  • natural products
  • synthetic antivirals
  • anticancer therapeutics

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Published Papers (1 paper)

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Research

15 pages, 2221 KiB  
Article
α-Methylacyl-CoA Racemase from Mycobacterium tuberculosis—Detailed Kinetic and Structural Characterization of the Active Site
by Otsile O. Mojanaga, Timothy J. Woodman, Matthew D. Lloyd and K. Ravi Acharya
Biomolecules 2024, 14(3), 299; https://doi.org/10.3390/biom14030299 - 02 Mar 2024
Viewed by 1110
Abstract
α-Methylacyl-CoA racemase in M. tuberculosis (MCR) has an essential role in fatty acid metabolism and cholesterol utilization, contributing to the bacterium’s survival and persistence. Understanding the enzymatic activity and structural features of MCR provides insights into its physiological and pathological significance and potential [...] Read more.
α-Methylacyl-CoA racemase in M. tuberculosis (MCR) has an essential role in fatty acid metabolism and cholesterol utilization, contributing to the bacterium’s survival and persistence. Understanding the enzymatic activity and structural features of MCR provides insights into its physiological and pathological significance and potential as a therapeutic target. Here, we report high-resolution crystal structures for wild-type MCR in a new crystal form (at 1.65 Å resolution) and for three active-site mutants, H126A, D156A and E241A, at 2.45, 1.64 and 1.85 Å resolutions, respectively. Our analysis of the new wild-type structure revealed a similar dimeric arrangement of MCR molecules to that previously reported and details of the catalytic site. The determination of the structures of these H126A, D156A and E241A mutants, along with their detailed kinetic analysis, has now allowed for a rigorous assessment of their catalytic properties. No significant change outside the enzymatic active site was observed in the three mutants, establishing that the diminution of catalytic activity is mainly attributable to disruption of the catalytic apparatus involving key hydrogen bonding and water-mediated interactions. The wild-type structure, together with detailed mutational and biochemical data, provide a basis for understanding the catalytic properties of this enzyme, which is important for the design of future anti-tuberculosis drug molecules. Full article
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