Molecular dynamics simulations of the bacterial periplasmic heme binding proteins ShuT and PhuT

Biophys Chem. 2008 Nov;138(1-2):42-9. doi: 10.1016/j.bpc.2008.09.001. Epub 2008 Sep 6.

Abstract

ShuT and PhuT are two periplasmic heme binding proteins that shuttle heme between the outer and inner membranes of the Gram-negative bacteria. Periplasmic binding proteins (PBPs) generally exhibit considerable conformational changes during the ligand binding process, whereas ShuT and PhuT belong to a class of PBPs that do not show such behavior based on their apo and holo crystal structures. By employing a series of molecular dynamic simulations on the ShuT and the PhuT, the dynamics and functions of the two PBPs were investigated. Through monitoring the distance changes between the two conserved glutamates of ShuT and PhuT, it was found the two PBPs were more flexible than previously assumed, exhibiting obvious opening-closing motions which were more remarkable in the apo runs of ShuT. Based on the results of the domain motion analysis, large scale conformational transitions were found in all apo runs of ShuT and PhuT, hinting that the domain motions of the two PBPs may be intrinsic. On the basis of the results of the principle component analysis, distinct opening-closing and twisting motion tendencies were observed not only in the apo, but also in the holo simulations of the two PBPs. The Gaussian network model was applied in order to analyze the hinge bending regions. The most important bending regions of ShuT and PhuT are located around the midpoints of their respective connecting helixes. Finally, the flexibilities and the details of the simulations of ShuT and PhuT were discussed. Characterized by the remarkably large flexibilities, the loop constituted by Ala 169, Gly170 and Gly171 of ShuT and the beta-turn constituted by Ala176, Gly177 and Gly178 of PhuT may be important for the functions of the two PBPs. Furthermore, the Asn254 of ShuT and the Arg228 of PhuT may be indispensable for the binding or unbinding of heme, since it is involved in the important hydrogen bonding to the propionate side-chains of heme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Computer Simulation
  • Heme / chemistry
  • Heme / metabolism*
  • Models, Molecular
  • Periplasmic Binding Proteins / chemistry*
  • Periplasmic Binding Proteins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary

Substances

  • Bacterial Proteins
  • Periplasmic Binding Proteins
  • Heme