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Interaction between Metal Compounds and Proteins 2.0
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Interaction between Metal Compounds and Proteins 2.0

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

Deadline for manuscript submissions: closed (20 April 2024) | Viewed by 3334

Special Issue Editor

Dr. Tomasz Frączyk

E-Mail Website
Guest Editor
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, Poland
Interests: bioinorganic chemistry; metal ion-protein complexes; metal ion–peptide complexes; posttranslational modifications; enzymology; protein dynamics; oxidative stress

Special Issue Information

Dear Colleagues,

Metal ions play many roles, ranging from physiological stabilization of native protein structure, through pathological induction of improper structure and aggregation of proteins or peptides, to structuring of the organic scaffold in metallodrugs. Thus, a thorough knowledge of the interaction of metal compounds with proteins is crucial for our understanding of physiology and pathology and allows us to design effective therapeutics or research tools.

Quantitative descriptions of binding strength, structural characterizations, and molecular simulations of metal compound–protein interactions are highly welcome. Research on biological and biochemical/biophysical activities of such complexes is also within the scope of this Special Issue. We encourage researchers working on these topics to submit research articles, communications, or reviews for this issue.

Dr. Tomasz Frączyk
Guest Editor

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

  • bioinorganic chemistry
  • metallodrugs
  • metalloproteins
  • metallopeptides
  • metal binding sites
  • metallomics

Related Special Issue

Published Papers (2 papers)

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Research

10 pages, 1990 KiB  
Communication
Chelator PBT2 Forms a Ternary Cu2+ Complex with β-Amyloid That Has High Stability but Low Specificity
by Simon C. Drew
Int. J. Mol. Sci. 2023, 24(11), 9267; https://doi.org/10.3390/ijms24119267 - 25 May 2023
Viewed by 989
Abstract
The metal chelator PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) acts as a terdentate ligand capable of forming binary and ternary Cu2+ complexes. It was clinically trialed as an Alzheimer’s disease (AD) therapy but failed to progress beyond phase II. The β-amyloid (Aβ) peptide associated with AD [...] Read more.
The metal chelator PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) acts as a terdentate ligand capable of forming binary and ternary Cu2+ complexes. It was clinically trialed as an Alzheimer’s disease (AD) therapy but failed to progress beyond phase II. The β-amyloid (Aβ) peptide associated with AD was recently concluded to form a unique Cu(Aβ) complex that is inaccessible to PBT2. Herein, it is shown that the species ascribed to this binary Cu(Aβ) complex in fact corresponds to ternary Cu(PBT2)NImAβ complexes formed by the anchoring of Cu(PBT2) on imine nitrogen (NIm) donors of His side chains. The primary site of ternary complex formation is His6, with a conditional stepwise formation constant at pH 7.4 (Kc [M−1]) of logKc = 6.4 ± 0.1, and a second site is supplied by His13 or His14 (logKc = 4.4 ± 0.1). The stability of Cu(PBT2)NImH13/14 is comparable with that of the simplest Cu(PBT2)NIm complexes involving the NIm coordination of free imidazole (logKc = 4.22 ± 0.09) and histamine (logKc = 4.00 ± 0.05). The 100-fold larger formation constant for Cu(PBT2)NImH6 indicates that outer-sphere ligand–peptide interactions strongly stabilize its structure. Despite the relatively high stability of Cu(PBT2)NImH6, PBT2 is a promiscuous chelator capable of forming a ternary Cu(PBT2)NIm complex with any ligand containing an NIm donor. These ligands include histamine, L-His, and ubiquitous His side chains of peptides and proteins in the extracellular milieu, whose combined effect should outweigh that of a single Cu(PBT2)NImH6 complex regardless of its stability. We therefore conclude that PBT2 is capable of accessing Cu(Aβ) complexes with high stability but low specificity. The results have implications for future AD therapeutic strategies and understanding the role of PBT2 in the bulk transport of transition metal ions. Given the repurposing of PBT2 as a drug for breaking antibiotic resistance, ternary Cu(PBT2)NIm and analogous Zn(PBT2)NIm complexes may be relevant to its antimicrobial properties. Full article
(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins 2.0)
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25 pages, 9040 KiB  
Article
Zn2+ and Cu2+ Interaction with the Recognition Interface of ACE2 for SARS-CoV-2 Spike Protein
by Alessio Pelucelli, Massimiliano Peana, Bartosz Orzeł, Karolina Piasta, Elzbieta Gumienna-Kontecka, Serenella Medici and Maria Antonietta Zoroddu
Int. J. Mol. Sci. 2023, 24(11), 9202; https://doi.org/10.3390/ijms24119202 - 24 May 2023
Cited by 1 | Viewed by 1702
Abstract
The spike protein (S) of SARS-CoV-2 is able to bind to the human angiotensin-converting enzyme 2 (ACE2) receptor with a much higher affinity compared to other coronaviruses. The binding interface between the ACE2 receptor and the spike protein plays a critical role in [...] Read more.
The spike protein (S) of SARS-CoV-2 is able to bind to the human angiotensin-converting enzyme 2 (ACE2) receptor with a much higher affinity compared to other coronaviruses. The binding interface between the ACE2 receptor and the spike protein plays a critical role in the entry mechanism of the SARS-CoV-2 virus. There are specific amino acids involved in the interaction between the S protein and the ACE2 receptor. This specificity is critical for the virus to establish a systemic infection and cause COVID-19 disease. In the ACE2 receptor, the largest number of amino acids playing a crucial role in the mechanism of interaction and recognition with the S protein is located in the C-terminal part, which represents the main binding region between ACE2 and S. This fragment is abundant in coordination residues such as aspartates, glutamates, and histidine that could be targeted by metal ions. Zn2+ ions bind to the ACE2 receptor in its catalytic site and modulate its activity, but it could also contribute to the structural stability of the entire protein. The ability of the human ACE2 receptor to coordinate metal ions, such as Zn2+, in the same region where it binds to the S protein could have a crucial impact on the mechanism of recognition and interaction of ACE2–S, with consequences on their binding affinity that deserve to be investigated. To test this possibility, this study aims to characterize the coordination ability of Zn2+, and also Cu2+ for comparison, with selected peptide models of the ACE2 binding interface using spectroscopic and potentiometric techniques. Full article
(This article belongs to the Special Issue Interaction between Metal Compounds and Proteins 2.0)
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