Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
NMR and molecular dynamics studies of the hydration of a zinc finger-DNA complex
Autore:
Tsui, V; Radhakrishnan, I; Wright, PE; Case, DA;
Indirizzi:
Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA Scripps Res Inst La Jolla CA USA 92037 t Mol Biol, La Jolla, CA 92037 USA
Titolo Testata:
JOURNAL OF MOLECULAR BIOLOGY
fascicolo: 5, volume: 302, anno: 2000,
pagine: 1101 - 1117
SICI:
0022-2836(20001006)302:5<1101:NAMDSO>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAGNETIC-RELAXATION DISPERSION; PANCREATIC TRYPSIN-INHIBITOR; TRANSCRIPTION FACTOR IIIA; INTERNAL WATER-MOLECULES; AQUEOUS-SOLUTION; PROTEIN HYDRATION; PROTON-EXCHANGE; BINDING DOMAIN; TRP OPERATOR; RECOGNITION;
Keywords:
TFIIIA; hydration; protein-DNA recognition; molecular dynamics simulations; zinc finger;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Wright, PE Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA ScrippsRes Inst La Jolla CA USA 92037 La Jolla, CA 92037 USA
Citazione:
V. Tsui et al., "NMR and molecular dynamics studies of the hydration of a zinc finger-DNA complex", J MOL BIOL, 302(5), 2000, pp. 1101-1117

Abstract

The hydration of a high-affinity protein-DNA complex involving the three amino terminal zinc finger domains of transcription factor IIIA (TFIIIA) anda 15-base-pair DNA duplex was investigated by NMR spectroscopy and molecular dynamics (MD) simulations. Intermolecular nuclear Overhauser effects (NOEs) between protein and water provided an experimental basis for identifying potential sites of hydration. These initial assignments were evaluated with the aid of two, 2 ns MD simulations of the protein-DNA complex conductedwith the explicit inclusion of water solvent. The two independent simulations produced similar trends in terms of water residence times around the solute, and these results were used to separate protein-water NOEs from alternate exchange-relayed cross peaks. Furthermore, only six of the 170 protonswhich failed to show intermolecular NOEs to solvent showed nearby long-resident water molecules in the MD simulations, illustrating an impressive level of agreement between theory and experiment. Analyses of the MD trajectories also allowed an examination of the role of water in recognition and binding affinity of the zinc fingers with DNA. The interface is well hydrated,characterized by direct contacts between the protein and DNA, as well as mediating water bridges. Approximately 18 water-mediated hydrogen bonds between the protein and DNA were observed on average. Roughly half of these were water molecules with long residence times that are most likely to be important for binding, since they involve residues which have been shown through biochemical studies to be crucial for protein-DNA binding. This level of atomic detail could not otherwise be established through the existing NMR and crystal structures of the TFIIIA-DNA complex. (C) 2000 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 20:18:01