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Structural-dynamical investigation of the ZnuA histidine-rich loop: involvement in zinc management and transport.

TitleStructural-dynamical investigation of the ZnuA histidine-rich loop: involvement in zinc management and transport.
Publication TypeJournal Article
Year of Publication2011
AuthorsFalconi, M, Oteri, F, Di Palma, F, Pandey, S, Battistoni, A, Desideri, A
JournalJ Comput Aided Mol Des
Date Published2011 Feb
KeywordsATP-Binding Cassette Transporters, Binding Sites, Biological Transport, Active, Carrier Proteins, Cation Transport Proteins, Crystallography, X-Ray, Escherichia coli Proteins, Histidine, Molecular Dynamics Simulation, Protein Binding, Structure-Activity Relationship, X-Ray Diffraction, Zinc

Comparative homology modelling techniques have been used to model the protein ZnuA from Salmonella enterica serovar Typhimurium using the 3D structure of the homologous protein from Escherichia coli. These two-domain proteins bind one Zn(2+) atom, with high affinity, in the inter-domain cleft and possess a histidine-rich loop in the N-terminal domain. Alternative structures of the ZnuA histidine-rich loop, never resolved by the X-ray diffraction method, have been modelled. A model of the apo form, one with the histidine-rich loop deleted and two alternative structures with a second zinc ion bound to the histidine-rich loop, have been generated. In all the modelled proteins, investigated through molecular dynamics simulation, the histidine-rich loop is highly mobile and its fluctuations are correlated to the ligand stability observed in the zinc sites. Based on the plasticity of the histidine-rich loop and its significant effects on protein mobility a possible role in the capture and/or transfer of the zinc ions has been suggested.

Alternate JournalJ. Comput. Aided Mol. Des.
PubMed ID21240623

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