LIVIVO - Search results -

Search results

Result 1 - 10 of total 99

Search options

Article ; Online: The avidin-theophylline complex: A structural and computational study.

Spinello, Angelo / Lapenta, Fabio / De March, Matteo

2023 Volume 91, Issue 10, Page(s) 1437–1443

Abstract: The interaction between avidin and its counterpart biotin is one of central importance in biology and has been reproposed and studied at length. However, the binding pocket of avidin is prone to promiscuous binding, able to accommodate even non- ... ...

Abstract	The interaction between avidin and its counterpart biotin is one of central importance in biology and has been reproposed and studied at length. However, the binding pocket of avidin is prone to promiscuous binding, able to accommodate even non-biotinylated ligands. Comprehending the factors that distinguish the extremely strong interaction with biotin to other ligands is an important step to fully picture the thermodynamics of these low-affinity complexes. Here, we present the complex between chicken white egg avidin and theophylline (TEP), the xanthine derivative used in the therapy of asthma. In the crystal structure, TEP lies in the biotin-binding pocket with the same orientation and planarity of the aromatic ring of 8-oxodeoxyguanosine. Indeed, its affinity for avidin measured by isothermal titration calorimetry is in the same μM range as those obtained for the previously characterized nucleoside derivatives. By the use of molecular dynamic simulations, we have investigated the most important intermolecular interactions occurring in the avidin-TEP binding pocket and compared them with those obtained for the avidin 8-oxodeoxyguanosine and avidin-biotin complexes. These results testify the capability of avidin to complex purely aromatic molecules.
MeSH term(s)	Avidin/chemistry ; Avidin/metabolism ; Biotin/chemistry ; Biotin/metabolism ; Theophylline ; Ligands ; Thermodynamics
Chemical Substances	Avidin (1405-69-2) ; Biotin (6SO6U10H04) ; Theophylline (C137DTR5RG) ; Ligands
Language	English
Publishing date	2023-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	806683-8
ISSN	1097-0134 ; 0887-3585
ISSN (online)	1097-0134
ISSN	0887-3585
DOI	10.1002/prot.26538
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2291: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Cancer-Related Mutations Alter RNA-Driven Functional Cross-Talk Underlying Premature-Messenger RNA Recognition by Splicing Factor SF3b.

Spinello, Angelo / Janos, Pavel / Rozza, Riccardo / Magistrato, Alessandra

The journal of physical chemistry letters

2023 Volume 14, Issue 27, Page(s) 6263–6269

Abstract: The pillar of faithful premature-messenger (pre-mRNA) splicing is the precise recognition of key intronic sequences by specific splicing factors. The heptameric splicing factor 3b (SF3b) recognizes the branch point sequence (BPS), a key part of the 3' ... ...

Abstract	The pillar of faithful premature-messenger (pre-mRNA) splicing is the precise recognition of key intronic sequences by specific splicing factors. The heptameric splicing factor 3b (SF3b) recognizes the branch point sequence (BPS), a key part of the 3' splice site. SF3b contains SF3B1, a protein holding recurrent cancer-associated mutations. Among these, K700E, the most-frequent SF3B1 mutation, triggers aberrant splicing, being primarily implicated in hematologic malignancies. Yet, K700E and the BPS recognition site are 60 Å apart, suggesting the existence of an allosteric cross-talk between the two distal spots. Here, we couple molecular dynamics simulations and dynamical network theory analysis to unlock the molecular terms underpinning the impact of SF3b splicing factor mutations on pre-mRNA selection. We establish that by weakening and remodeling interactions of pre-mRNA with SF3b, K700E scrambles RNA-mediated allosteric cross-talk between the BPS and the mutation site. We propose that the altered allostery contributes to cancer-associated missplicing by mutated SF3B1. This finding broadens our comprehension of the elaborate mechanisms underlying pre-mRNA metabolism in eukaryotes.
MeSH term(s)	Humans ; RNA Splicing Factors/genetics ; RNA Splicing Factors/metabolism ; RNA, Messenger ; RNA Precursors/genetics ; RNA Precursors/metabolism ; RNA ; Mutation ; Neoplasms/genetics ; Transcription Factors
Chemical Substances	RNA Splicing Factors ; RNA, Messenger ; RNA Precursors ; RNA (63231-63-0) ; Transcription Factors
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Journal Article
ISSN	1948-7185
ISSN (online)	1948-7185
DOI	10.1021/acs.jpclett.3c01402
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Role of computational and structural biology in the development of small-molecule modulators of the spliceosome.

Rozza, Riccardo / Janoš, Pavel / Spinello, Angelo / Magistrato, Alessandra

Expert opinion on drug discovery

2022 Volume 17, Issue 10, Page(s) 1095–1109

Abstract: Introduction: RNA splicing is a pivotal step of eukaryotic gene expression during which the introns are excised from the precursor (pre-)RNA and the exons are joined together to form mature RNA products (i.e a protein-coding mRNA or long non-coding (lnc) ...

Abstract	Introduction: RNA splicing is a pivotal step of eukaryotic gene expression during which the introns are excised from the precursor (pre-)RNA and the exons are joined together to form mature RNA products (i.e a protein-coding mRNA or long non-coding (lnc)RNAs). The spliceosome, a complex ribonucleoprotein machine, performs pre-RNA splicing with extreme precision. Deregulated splicing is linked to cancer, genetic, and neurodegenerative diseases. Hence, the discovery of small-molecules targeting core spliceosome components represents an appealing therapeutic opportunity. Area covered: Several atomic-level structures of the spliceosome and distinct splicing-modulators bound to its protein/RNA components have been solved. Here, we review recent advances in the discovery of small-molecule splicing-modulators, discuss opportunities and challenges for their therapeutic applicability, and showcase how structural data and/or all-atom simulations can illuminate key facets of their mechanism, thus contributing to future drug-discovery campaigns. Expert opinion: This review highlights the potential of modulating pre-RNA splicing with small-molecules, and anticipates how the synergy of computer and wet-lab experiments will enrich our understanding of splicing regulation/deregulation mechanisms. This information will aid future structure-based drug-discovery efforts aimed to expand the currently limited portfolio of selective splicing-modulators.
MeSH term(s)	Humans ; Introns ; RNA Precursors/chemistry ; RNA Precursors/genetics ; RNA Precursors/metabolism ; RNA Splicing ; Spliceosomes/chemistry ; Spliceosomes/genetics ; Spliceosomes/metabolism
Chemical Substances	RNA Precursors
Language	English
Publishing date	2022-08-24
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	2259618-5
ISSN	1746-045X ; 1746-0441
ISSN (online)	1746-045X
ISSN	1746-0441
DOI	10.1080/17460441.2022.2114452
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6388: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: How the Metal Ion Affects the

Butera, Valeria / D'Anna, Luisa / Rubino, Simona / Bonsignore, Riccardo / Spinello, Angelo / Terenzi, Alessio / Barone, Giampaolo

The journal of physical chemistry. A

2023 Volume 127, Issue 44, Page(s) 9283–9290

Abstract: The chemical shift (CS) values obtained ... ...

Abstract	The chemical shift (CS) values obtained by
Language	English
Publishing date	2023-10-31
Publishing country	United States
Document type	Journal Article
ISSN	1520-5215
ISSN (online)	1520-5215
DOI	10.1021/acs.jpca.3c05653
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Novel half Salphen cobalt(III) complexes: synthesis, DNA binding and anticancer studies.

Bonsignore, Riccardo / Trippodo, Elisa / Di Gesù, Roberto / Carreca, Anna Paola / Rubino, Simona / Spinello, Angelo / Terenzi, Alessio / Barone, Giampaolo

Dalton transactions (Cambridge, England : 2003)

2024 Volume 53, Issue 14, Page(s) 6311–6322

Abstract: While platinum(II)-based drugs continue to be employed in cancer treatments, the escalating occurrence of severe side effects has spurred researchers to explore novel sources for potential therapeutic agents. Notably, cobalt(III) has emerged as a subject ...

Abstract	While platinum(II)-based drugs continue to be employed in cancer treatments, the escalating occurrence of severe side effects has spurred researchers to explore novel sources for potential therapeutic agents. Notably, cobalt(III) has emerged as a subject of considerable interest due to its ubiquitous role in human physiology. Several studies investigating the anticancer effects of Salphen complexes derived from cobalt(III) have unveiled intriguing antiproliferative properties. In a bid to enhance our understanding of this class of compounds, we synthesized and characterized two novel half Salphen cobalt(III) complexes. Both compounds exhibited notable stability, even in the presence of physiologically relevant concentrations of glutathione. The application of spectroscopic and computational methodologies unravelled their interactions with duplex and G4-DNAs, suggesting an external binding affinity for these structures, with preliminary indications of selectivity trends. Importantly, antiproliferative assays conducted on 3D cultured SW-1353 cancer cells unveiled a compelling anticancer activity at low micromolar concentrations, underscoring the potential therapeutic efficacy of this novel class of cobalt(III) complexes.
MeSH term(s)	Humans ; Coordination Complexes/chemistry ; Cobalt/pharmacology ; Cobalt/chemistry ; Phenylenediamines/chemistry ; DNA/chemistry ; Antineoplastic Agents/chemistry
Chemical Substances	Coordination Complexes ; salphen ; Cobalt (3G0H8C9362) ; Phenylenediamines ; DNA (9007-49-2) ; Antineoplastic Agents
Language	English
Publishing date	2024-04-02
Publishing country	England
Document type	Journal Article
ZDB-ID	1472887-4
ISSN	1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
ISSN (online)	1477-9234 ; 1364-5447
ISSN	0300-9246 ; 1477-9226
DOI	10.1039/d4dt00092g
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Anticancer Activity, Reduction Mechanism and G-Quadruplex DNA Binding of a Redox-Activated Platinum(IV)-Salphen Complex.

Vigna, Vincenzo / Scoditti, Stefano / Spinello, Angelo / Mazzone, Gloria / Sicilia, Emilia

International journal of molecular sciences

2022 Volume 23, Issue 24

Abstract: Aiming at reducing the unselective cytotoxicity of Pt(II) chemotherapeutics, a great deal of effort has been concentrated into the design of metal-containing drugs with different anticancer mechanisms of action. Inert Pt(IV) prodrugs have been proposed ... ...

Abstract	Aiming at reducing the unselective cytotoxicity of Pt(II) chemotherapeutics, a great deal of effort has been concentrated into the design of metal-containing drugs with different anticancer mechanisms of action. Inert Pt(IV) prodrugs have been proposed to be a valid alternative as they are activated by reduction directly into the cell releasing active Pt(II) species. On the other hand, a promising strategy for designing metallodrugs is to explore new potential biological targets rather than canonical B-DNA. G-quadruplex nucleic acid, obtained by self-assembly of guanine-rich nucleic acid sequences, has recently been considered an attractive target for anticancer drug design. Therefore, compounds capable of binding and stabilizing this type of DNA structure would be greatly beneficial in anticancer therapy. Here, computational analysis reports the mechanism of action of a recently synthesized Pt(IV)-salphen complex conjugating the inertness of Pt(IV) prodrugs with the ability to bind G-quadruplexes of the corresponding Pt(II) complex. The reduction mechanism of the Pt(IV) complex with a biological reducing agent was investigated in depth by means of DFT, whereas classical MD simulations were carried out to shed light into the binding mechanism of the released Pt(II) complex. The results show that the Pt(IV) prodrug may be reduced by both inner- and outer-sphere mechanisms, and the active Pt(II) complex, as a function of its protonation state, stabilizes the G-quadruplex DNA prevalently, either establishing π-stacking interactions with the terminal G-tetrad or through electrostatic interactions along with H-bonds formation.
Language	English
Publishing date	2022-12-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232415579
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Molecular Basis of SARS-CoV-2 Nsp1-Induced Immune Translational Shutdown as Revealed by All-Atom Simulations.

Borišek, Jure / Spinello, Angelo / Magistrato, Alessandra

The journal of physical chemistry letters

2021 Volume 12, Issue 48, Page(s) 11745–11750

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents the most severe global health crisis in modern human history. One of the major SARS-CoV-2 virulence factors is nonstructural protein 1 (Nsp1), which, outcompeting with ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents the most severe global health crisis in modern human history. One of the major SARS-CoV-2 virulence factors is nonstructural protein 1 (Nsp1), which, outcompeting with the binding of host mRNA to the human ribosome, triggers a translation shutdown of the host immune system. Here, microsecond-long all-atom simulations of the C-terminal portion of the SARS-CoV-2/SARS-CoV Nsp1 in complex with the 40S ribosome disclose that SARS-CoV-2 Nsp1 has evolved from its SARS-CoV ortholog to more effectively hijack the ribosome by undergoing a critical switch of Q/E158 and E/Q159 residues that perfects Nsp1's interactions with the ribosome. Our outcomes offer a basis for understanding the sophisticated mechanisms underlying SARS-CoV-2 diversion and exploitation of human cell components to its deadly purposes.
MeSH term(s)	COVID-19/immunology ; COVID-19/pathology ; COVID-19/virology ; Humans ; Hydrogen Bonding ; Molecular Dynamics Simulation ; Protein Binding ; Ribosome Subunits, Small, Eukaryotic/chemistry ; Ribosome Subunits, Small, Eukaryotic/metabolism ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/metabolism ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/metabolism
Chemical Substances	NSP1 protein, SARS-CoV-2 ; Viral Nonstructural Proteins
Language	English
Publishing date	2021-12-01
Publishing country	United States
Document type	Journal Article
ISSN	1948-7185
ISSN (online)	1948-7185
DOI	10.1021/acs.jpclett.1c03441
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Allosteric Cross-Talk among Spike's Receptor-Binding Domain Mutations of the SARS-CoV-2 South African Variant Triggers an Effective Hijacking of Human Cell Receptor.

Spinello, Angelo / Saltalamacchia, Andrea / Borišek, Jure / Magistrato, Alessandra

The journal of physical chemistry letters

2021 Volume 12, Issue 25, Page(s) 5987–5993

Abstract: The rapid and relentless emergence of novel highly transmissible SARS-CoV-2 variants, possibly decreasing vaccine efficacy, currently represents a formidable medical and societal challenge. These variants frequently hold mutations on the Spike protein's ... ...

Abstract	The rapid and relentless emergence of novel highly transmissible SARS-CoV-2 variants, possibly decreasing vaccine efficacy, currently represents a formidable medical and societal challenge. These variants frequently hold mutations on the Spike protein's receptor-binding domain (RBD), which, binding to the angiotensin-converting enzyme 2 (ACE2) receptor, mediates viral entry into host cells. Here, all-atom molecular dynamics simulations and dynamical network theory of the wild-type and mutant RBD/ACE2 adducts disclose that while the N501Y mutation (UK variant) enhances the Spike's binding affinity toward ACE2, the concomitant N501Y, E484K, and K417N mutations (South African variant) aptly adapt to increase SARS-CoV-2 propagation via a two-pronged strategy: (i) effectively grasping ACE2 through an allosteric signaling between pivotal RBD structural elements and (ii) impairing the binding of antibodies elicited by infected or vaccinated patients. This information unlocks the molecular terms and evolutionary strategies underlying the increased virulence of emerging SARS-CoV-2 variants, setting the basis for developing the next-generation anti-COVID-19 therapeutics.
MeSH term(s)	Angiotensin-Converting Enzyme 2/chemistry ; Angiotensin-Converting Enzyme 2/metabolism ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/metabolism ; Humans ; Molecular Dynamics Simulation ; Mutation ; Protein Binding/genetics ; Protein Domains/genetics ; SARS-CoV-2/chemistry ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Thermodynamics
Chemical Substances	Antibodies, Monoclonal ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-06-23
Publishing country	United States
Document type	Journal Article
ISSN	1948-7185
ISSN (online)	1948-7185
DOI	10.1021/acs.jpclett.1c01415
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.

Spinello, Angelo / Borišek, Jure / Malcovati, Luca / Magistrato, Alessandra

International journal of molecular sciences

2021 Volume 22, Issue 20

Abstract: The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of ... ...

Abstract	The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long all-atom simulations addressed the binding/dissociation mechanism of H3B-8800 to wild type and K700E SF3B1-containing SF3b (
MeSH term(s)	Humans ; Molecular Dynamics Simulation ; Mutation ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Phenotype ; Phosphoproteins/chemistry ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Piperazines/chemistry ; Piperazines/metabolism ; Protein Conformation ; Pyridines/chemistry ; Pyridines/metabolism ; RNA Splicing ; RNA Splicing Factors/chemistry ; RNA Splicing Factors/genetics ; RNA Splicing Factors/metabolism
Chemical Substances	H3B-8800 ; Phosphoproteins ; Piperazines ; Pyridines ; RNA Splicing Factors ; SF3B1 protein, human
Language	English
Publishing date	2021-10-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222011222
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Frontiers of metal-coordinating drug design.

Palermo, Giulia / Spinello, Angelo / Saha, Aakash / Magistrato, Alessandra

Expert opinion on drug discovery

2020 Volume 16, Issue 5, Page(s) 497–511

Abstract: Introduction: ...

Abstract	Introduction:
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/chemistry ; Chemistry, Pharmaceutical/methods ; Computer Simulation ; Coordination Complexes/chemistry ; Drug Design ; Drug Discovery/methods ; Humans ; Ligands ; Metals/chemistry ; Metals/metabolism
Chemical Substances	Antineoplastic Agents ; Coordination Complexes ; Ligands ; Metals
Language	English
Publishing date	2020-12-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2259618-5
ISSN	1746-045X ; 1746-0441
ISSN (online)	1746-045X
ISSN	1746-0441
DOI	10.1080/17460441.2021.1851188
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 6388: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito