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

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Abstract

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 Zn2+ 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.

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Acknowledgments

The authors thank professor E. Chiancone for her interest, the reading of the manuscript and the helpful comments. This work was partially supported by a grant from the Fondazione Roma. O.F. thanks Filas for a fellowship granted under the project “Caratterizzazione di principi attivi”.

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Authors and Affiliations

  1. Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133, Rome, Italy

    Mattia Falconi, Francesco Oteri, Francesco Di Palma, Saurabh Pandey, Andrea Battistoni & Alessandro Desideri

  2. CIBB, Center of Biostatistics and Bioinformatics, Via della Ricerca Scientifica, 00133, Rome, Italy

    Mattia Falconi, Francesco Oteri & Alessandro Desideri

  3. Interuniversity Consortium, National Institute Biostructure and Biosystem (INBB), Rome, Italy

    Mattia Falconi & Alessandro Desideri

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  1. Mattia Falconi
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Correspondence to Mattia Falconi.

Electronic supplementary material

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10822_2010_9409_MOESM1_ESM.tif

Fig. 1s Time evolution of total solvent accessible surface area in the Loop1, Loop2, Apo, dLoop, DZn1 and DZn2 Se-ZnuA trajectories. Supplementary material 1 (TIFF 2931 kb)

10822_2010_9409_MOESM2_ESM.tif

Fig. 2s Time evolution of gyration radius in the Loop1, Loop2, Apo, dLoop, DZn1 and DZn2 Se-ZnuA trajectories. Supplementary material 2 (TIFF 2931 kb)

10822_2010_9409_MOESM3_ESM.tif

Fig. 3s Time evolution of number of residues in α and β secondary structures in the Loop1, Loop2, Apo, dLoop, DZn1 and DZn2 Se-ZnuA trajectories. Supplementary material 3 (TIFF 2931 kb)

10822_2010_9409_MOESM4_ESM.tif

Fig. 4s Time evolution of total number of hydrogen bonds in the Loop1, Loop2, Apo, dLoop, DZn1 and DZn2 Se-ZnuA trajectories. Supplementary material 4 (TIFF 2931 kb)

10822_2010_9409_MOESM5_ESM.tif

Fig. 5s Solvent accessible surface area of the primary zinc site calculated for Loop1, Loop2, Apo, dLoop, DZn1 and DZn2 Se-ZnuA trajectories. The solvent exposed atoms within 10 Å from the zinc ion have been selected for the calculation in all the simulated systems containing the metal. In the Apo simulation, due to the absence of zinc, the Nε2 atom of the His124, a ligand in the other simulations, has been chosen as calculation center. Supplementary material 5 (TIFF 2931 kb)

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Falconi, M., Oteri, F., Di Palma, F. et al. Structural-dynamical investigation of the ZnuA histidine-rich loop: involvement in zinc management and transport. J Comput Aided Mol Des 25, 181–194 (2011). https://doi.org/10.1007/s10822-010-9409-6

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