Structural and functional analysis of the simultaneous binding of two duplex/quadruplex aptamers to human α-thrombin (122 views)
Int J Biol Macromol (ISSN: 0141-8130linking, 1879-0003electronic), 2021 Jun 30; 181: 858-867.
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Paper type: Journal Article,
Impact factor: 5.162, 5-year impact factor: 3.227
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Keywords: Anti-Thrombin Aptamer, Inter-Exosite Communication, Thrombin Modulation, Anticoagulants Pharmacology, Nucleotide Chemistry Metabolism, Blood Coagulation Drug Effects, Crystallography, X-Ray, Fibrinogen Metabolism, Humans, Molecular Dynamics Simulation, Protein Binding, Thrombin Chemistry Metabolism, Time Factors,
Affiliations:
*** IBB - CNR ***
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126 Naples, Italy.
Institute of Biostructures and Bioimaging, CNR, Naples I-80134, Italy.
References:
Not available.
Int J Biol Macromol (ISSN: 0141-8130linking, 1879-0003electronic), 2021 Jun 30; 181: 858-867.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 5.162, 5-year impact factor: 3.227
Url: Not available.
Keywords: Anti-Thrombin Aptamer, Inter-Exosite Communication, Thrombin Modulation, Anticoagulants Pharmacology, Nucleotide Chemistry Metabolism, Blood Coagulation Drug Effects, Crystallography, X-Ray, Fibrinogen Metabolism, Humans, Molecular Dynamics Simulation, Protein Binding, Thrombin Chemistry Metabolism, Time Factors,
Affiliations:
*** IBB - CNR ***
Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126 Naples, Italy.
Institute of Biostructures and Bioimaging, CNR, Naples I-80134, Italy.
References:
Not available.
Structural and functional analysis of the simultaneous binding of two duplex/quadruplex aptamers to human α-thrombin
The long-range communication between the two exosites of human α-thrombin (thrombin) tightly modulates the protein-effector interactions. Duplex/quadruplex aptamers represent an emerging class of very effective binders of thrombin. Among them, NU172 and HD22 aptamers are at the forefront of exosite I and II recognition, respectively. The present study investigates the simultaneous binding of these two aptamers by combining a structural and dynamics approach. The crystal structure of the ternary complex formed by the thrombin with NU172 and HD22_27mer provides a detailed view of the simultaneous binding of these aptamers to the protein, inspiring the design of novel bivalent thrombin inhibitors. The crystal structure represents the starting model for molecular dynamics studies, which point out the cooperation between the binding at the two exosites. In particular, the binding of an aptamer to its exosite reduces the intrinsic flexibility of the other exosite, that preferentially assumes conformations similar to those observed in the bound state, suggesting a predisposition to interact with the other aptamer. This behaviour is reflected in a significant increase of the anticoagulant activity of NU172 when the inactive HD22_27mer is bound to exosite II, providing a clear evidence of the synergic action of the two aptamers.
The long-range communication between the two exosites of human α-thrombin (thrombin) tightly modulates the protein-effector interactions. Duplex/quadruplex aptamers represent an emerging class of very effective binders of thrombin. Among them, NU172 and HD22 aptamers are at the forefront of exosite I and II recognition, respectively. The present study investigates the simultaneous binding of these two aptamers by combining a structural and dynamics approach. The crystal structure of the ternary complex formed by the thrombin with NU172 and HD22_27mer provides a detailed view of the simultaneous binding of these aptamers to the protein, inspiring the design of novel bivalent thrombin inhibitors. The crystal structure represents the starting model for molecular dynamics studies, which point out the cooperation between the binding at the two exosites. In particular, the binding of an aptamer to its exosite reduces the intrinsic flexibility of the other exosite, that preferentially assumes conformations similar to those observed in the bound state, suggesting a predisposition to interact with the other aptamer. This behaviour is reflected in a significant increase of the anticoagulant activity of NU172 when the inactive HD22_27mer is bound to exosite II, providing a clear evidence of the synergic action of the two aptamers.
Structural and functional analysis of the simultaneous binding of two duplex/quadruplex aptamers to human α-thrombin
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Structural and functional analysis of the simultaneous binding of two duplex/quadruplex aptamers to human α-thrombin
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Troisi R, Balasco N, Autiero I, Vitagliano L, Sica F
* Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands (74 views)
Int J Mol Sc (ISSN: 1422-0067linking, 1422-0067electronic, 1661-6596), 2021 Oct 6; 22 (19 ): N/D-N/D.
Impact Factor: 2.598
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Troisi R, Balasco N, Vitagliano L, Sica F
* Molecular dynamics simulations of human α-thrombin in different structural contexts: evidence for an aptamer-guided cooperation between the two exosites (133 views)
J Biomol Struct Dyn (ISSN: 0739-1102linking, 1538-0254electronic), 2021 Apr; 39(6): 2199-2209.
Impact Factor: 4.986
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Riccardi C, Napolitano E, Platella C, Musumeci D, Montesarchio D
* G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects (65 views)
Pharmacol Ther (ISSN: 0163-7258linking), 2021 Jan; 217: 107649-107649.
Impact Factor: 11.127
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Autiero I, Ruvo M, Improta R, Vitagliano L
* The intrinsic flexibility of the aptamer targeting the ribosomal protein S8 is a key factor for the molecular recognition (453 views)
Bba-Gen Subjects (ISSN: 0304-4165print, 0304-4165linking, 1872-8006electronic), 2018 Apr; 1862(4): 1006-1016.
Impact Factor: 3.829
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Pirone L, Ripoll-rozada J, Leone M, Ronca R, Lombardo F, Fiorentino G, Andersen JF, Pereira PJB, Arcà B, Pedone E
* Functional analyses yield detailedinsight into the mechanism of thrombin inhibition by the antihemostatic salivary protein cE5 from Anopheles gambiae (462 views) (PDF 204 views)
Jbc Papers (ISSN: 0021-9258linking, 1083-351x), 2017 Jul 28; 292(30): 12632-12642.
Impact Factor: 4.125
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Platella C, Riccardi C, Montesarchio D, Roviello GN, Musumeci D
* G-quadruplex-based aptamers against protein targets in therapy and diagnostics (436 views)
Bba-Gen Subjects (ISSN: 0304-4165, 0006-3002, 1872-8006electronic), 2017 May; 1861(5PtB): 1429-1447.
Impact Factor: 3.679
View Export to BibTeX Export to EndNote
* Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands (74 views)
Int J Mol Sc (ISSN: 1422-0067linking, 1422-0067electronic, 1661-6596), 2021 Oct 6; 22 (19 ): N/D-N/D.
Impact Factor: 2.598
View Export to BibTeX Export to EndNote
Troisi R, Balasco N, Vitagliano L, Sica F
* Molecular dynamics simulations of human α-thrombin in different structural contexts: evidence for an aptamer-guided cooperation between the two exosites (133 views)
J Biomol Struct Dyn (ISSN: 0739-1102linking, 1538-0254electronic), 2021 Apr; 39(6): 2199-2209.
Impact Factor: 4.986
View Export to BibTeX Export to EndNote
Riccardi C, Napolitano E, Platella C, Musumeci D, Montesarchio D
* G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects (65 views)
Pharmacol Ther (ISSN: 0163-7258linking), 2021 Jan; 217: 107649-107649.
Impact Factor: 11.127
View Export to BibTeX Export to EndNote
Autiero I, Ruvo M, Improta R, Vitagliano L
* The intrinsic flexibility of the aptamer targeting the ribosomal protein S8 is a key factor for the molecular recognition (453 views)
Bba-Gen Subjects (ISSN: 0304-4165print, 0304-4165linking, 1872-8006electronic), 2018 Apr; 1862(4): 1006-1016.
Impact Factor: 3.829
View Export to BibTeX Export to EndNote
Pirone L, Ripoll-rozada J, Leone M, Ronca R, Lombardo F, Fiorentino G, Andersen JF, Pereira PJB, Arcà B, Pedone E
* Functional analyses yield detailedinsight into the mechanism of thrombin inhibition by the antihemostatic salivary protein cE5 from Anopheles gambiae (462 views) (PDF 204 views)
Jbc Papers (ISSN: 0021-9258linking, 1083-351x), 2017 Jul 28; 292(30): 12632-12642.
Impact Factor: 4.125
View Export to BibTeX Export to EndNote
Platella C, Riccardi C, Montesarchio D, Roviello GN, Musumeci D
* G-quadruplex-based aptamers against protein targets in therapy and diagnostics (436 views)
Bba-Gen Subjects (ISSN: 0304-4165, 0006-3002, 1872-8006electronic), 2017 May; 1861(5PtB): 1429-1447.
Impact Factor: 3.679
View Export to BibTeX Export to EndNote
6 Records (5 excluding Abstracts).
Total impact factor: 30.344 (26.665 excluding Abstracts).
Total 5 year impact factor: 27.653 (22.843 excluding Abstracts).
Total impact factor: 30.344 (26.665 excluding Abstracts).
Total 5 year impact factor: 27.653 (22.843 excluding Abstracts).
122 views. Last view on Monday 07 October 2024, 15:38:46
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