Channel blocking of MspA revisited

Langmuir. 2013 Jan 8;29(1):308-15. doi: 10.1021/la3037296. Epub 2012 Dec 13.

Abstract

Porin A from Mycobacterium smegmatis (MspA) is a highly stable, octameric channel protein, which acts as the main transporter of electrolytes across the cell membrane. MspA features a narrow, negatively charged constriction zone, allowing stable binding of various analytes thereby blocking the channel. Investigation of channel blocking of mycobacterial porins is of significance in developing alternate treatment methods for tuberculosis. The concept that ruthenium(II)quaterpyridinium complexes have the capability to act as efficient channel blockers for MspA and related porins, emerged after very high binding constants were measured by high-performance liquid chromatography and steady-state luminescence studies. Consequently, the interactions between the ruthenium(II) complex RuC2 molecules and MspA, leading to RuC2@MspA assemblies, have been studied utilizing time-resolved absorption/emission, atomic force microscopy, dynamic light scattering, ζ potential measurements, and isothermal titration calorimetry. The results obtained provide evidence for the formation of clusters/large aggregates of RuC2 and MspA. The results are of interest with respect to utilizing prospective channel blockers in porins. The combination of results from conceptually different techniques shed some light onto the chemical nature of MspA-channel blocker interactions thus contributing to the development of a paradigm for channel blocking.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Calorimetry
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology
  • Fluorescence
  • Membrane Transport Modulators / chemistry
  • Membrane Transport Modulators / metabolism*
  • Microscopy, Atomic Force
  • Models, Biological
  • Molecular Structure
  • Mycobacterium smegmatis*
  • Nanostructures / chemistry
  • Porins / chemistry*
  • Porins / drug effects
  • Porins / metabolism
  • Ruthenium / chemistry*
  • Temperature

Substances

  • Coordination Complexes
  • Membrane Transport Modulators
  • Porins
  • mspA protein, Mycobacterium smegmatis
  • Ruthenium