Binding of Zn(II) to Tropomyosin Receptor Kinase A in Complex with Its Cognate Nerve Growth Factor: Insights from Molecular Simulation and in Vitro Essays
Binding of Zn(II) to Tropomyosin Receptor Kinase A in Complex with Its Cognate Nerve Growth Factor: Insights from Molecular Simulation and in Vitro Essays(201 views visite) Pietropaolo A, Magri A, Greco V, Losasso V, La Mendola D, Sciuto S, Carloni P, Rizzarelli E
Keywords Parole chiave: Metadynamics Simulation, Metal Complexes, Metal Ions, Neurotrophin, Peptide,
Affiliations Affiliazioni: *** IBB - CNR ***
Dipartimento di Scienze della Salute, Universita di Catanzaro , Viale Europa, 88100 Catanzaro, Italy., IBB-CNR , UOS Catania, via Paolo Gaifami 18, 95126 Catania, Italy., Dipartimento di Scienze Chimiche, Universita degli Studi di Catania , Viale Andrea Doria 6, 95125 Catania, Italy., Institute for Computational Biomedicine (IAS-5/INM-9/INM-9) Forschungszentrum Julich , 52425 Julich, Germany., Department of Physics, RWTH Aachen University , 52056 Aachen, Germany., Department of Pharmacy, University of Pisa , Via Bonanno Pisano 6, 56126 Pisa, Italy.,
References Riferimenti: Not available. Non disponibili.
Binding of Zn(II) to Tropomyosin Receptor Kinase A in Complex with Its Cognate Nerve Growth Factor: Insights from Molecular Simulation and in Vitro Essays
The binding of the human nerve growth factor (NGF) protein to tropomyosin receptor kinase A (TrkA) is associated with Alzhemeir's development. Owing to the large presence of zinc(II) ions in the synaptic compartments, the zinc ions might be bound to the complex in vivo. Here, we have identified a putative zinc binding site using a combination of computations and experiments. First, we have predicted structural features of the NGF/TrkA complex in an aqueous solution by molecular simulation. Metadynamics free energy calculations suggest that these are very similar to those in the X-ray structure. Here, the "crab" structure of the NGF shape binds tightly to two TrkA "pincers". Transient conformations of the complex include both more extended and more closed conformations. Interestingly, the latter features facial histidines (His60 and His61) among the N-terminal D1-D3 domains, each of which is a potential binding region for biometals. This suggests the presence of a four-His Zn binding site connecting the two chains. To address this issue, we investigated the binding of a D1-D3 domains' peptide mimic by stability constant and nuclear magnetic resonance measurements, complemented by density functional theory-based calculations. Taken together, these establish unambiguously a four-His coordination of the metal ion in the model systems, supporting the presence of our postulated binding site in the NGF/TrkA complex.
Binding of Zn(II) to Tropomyosin Receptor Kinase A in Complex with Its Cognate Nerve Growth Factor: Insights from Molecular Simulation and in Vitro Essays
Binding of Zn(II) to Tropomyosin Receptor Kinase A in Complex with Its Cognate Nerve Growth Factor: Insights from Molecular Simulation and in Vitro Essays
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(390 visite) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 DettagliEsporta in BibTeXEsporta in EndNote
Testino G, Leone S, Fagoonee S, Del Bas JM, Rodriguez B, Puiggros F, Marine S, Rodriguez MA, Morina D, Armengol L, Caimari A, Arola L, Cimini FA, Barchetta I, Carotti S, Bertoccini L, Baroni MG, Vespasiani-gentilucci U, Cavallo MG, Morini S, Nelson JE, Roth CL, Wilson LA, Yates KP, Aouizerat B, Morgan-stevenson V, Whalen E, Hoofnagle A, Mason M, Gersuk V, Yeh MM, Kowdley KV, Lee SM, Jun DW, Cho YK, Jang KS, Kucukazman M, Ata N, Dal K, Yeniova AO, Kefeli A, Basyigit S, Aktas B, Akin KO, Agladioglu K, Ure OS, Topal F, Nazligul Y, Beyan E, Ertugrul DT, Catena C, Cosma C, Camozzi V, Plebani M, Ermani M, Sechi LA, Fallo F, Goto Y, Ray MB, Mendenhall CL, French SW, Gartside PS Serum vitamin A deficiency and increased intrahepatic expression of cytokeratin antigen in alcoholic liver disease(467 visite) Hepatology (ISSN: 1827-1669electronic, 0026-4806linking), 1988 Sep; 83120693611123109(5): 1019-1026. Impact Factor:0.913 DettagliEsporta in BibTeXEsporta in EndNote
852 Records (777 escludendo Abstract e Conferenze). Impact factor totale: 2992.132 (2788.189 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 3126.18 (2906.607 escludendo Abstract e Conferenze).
Last modified by Ultima modifica di Massimiliano Sorbillo on in data Sunday 12 July 2020, 13:14:42 201 views visite. Last view on Ultima visita in data Sunday 28 March 2021, 23:04:43