Structural Chemistry

, Volume 29, Issue 2, pp 393–401 | Cite as

Quantum chemical calculations of the active site of the solute-binding protein PsaA from Streptococcus pneumoniae explain electronic selectivity of metal binding

  • Sergio Manzetti
Original Research


Streptococcus pneumoniae is the world’s foremost bacterial pathogen. Virulence in the host is dependent on manganese acquisition via the PsaBCA permease. Crystallographic studies of its solute-binding protein component, PsaA, have previously shown that the nature of the metal ion bound by the protein modulates the conformational changes associated with its function. Notably, manganese and cadmium ions can be bound in a reversible manner, facilitating transport via PsaA, whereas zinc binds in an essentially irreversible manner preventing release to the permease. All three ionic species show a similar coordination in the PsaA crystal structures. A set of quantum chemical calculations have here been performed in order to differentiate between the ions in terms of electronic configuration. Based on natural bond orbital (NBO) analysis, the results show that manganese and cadmium bind more strongly to the protein than zinc, in that their coordination to the enzyme involves more shared electrons. Manganese has the highest indirect indicator of bonding strength and provides an unpaired electron that induces the formation of three bonds to the enzyme active site. Cadmium binds more strongly than zinc, though more weakly than manganese, and forms only ionic bonds in its ligand framework. These calculations indicate a concrete differentiation of the bonding states of the three active sites; however, bonding energies which can give more accurate estimates have not been computed presently. The calculations further show that the ionic radii are critical for the bonding state between the enzyme and the metal and that the conformational motions responsible for the PsaA’s functional cycle may depend on the ion binding strongly to the enzyme. Our results add important information of the PsaA-metal ion binding architecture to the existing crystallography data and aid in understanding the function of this protein.


Streptococcus pneumoniae PsaA Quantum chemistry High-performance computing Natural bond orbitals 



The author would like to thank Prof Bostjan Kobe at the University of Queensland for suggesting this investigation and Dr. Megan O′ Mara at the University of Queensland and Chris McDewitt at the University of Adelaide, Australia, for the critical comments which have altogether been of invaluable assistance for this project. The author would also like to thank the referees for valuable comments during the revision process.

Funding information

This publication is part of the project number 264086, “Nanoactivities,” funded by the Norwegian Research Council, SkatteFUNN scheme.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Fjordforsk A/S, NanoFactoryVangsnesNorway
  2. 2.Computational Systems and BiologyUppsala UniversityUppsalaSweden

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