Insight into determinants of substrate binding and transport in a multidrug efflux protein


Autoria(s): Alegre, Kamela O.; Paul, Stephanie; Labarbuta, Paola; Law, Christopher J
Data(s)

10/03/2016

Resumo

<p>Multidrug resistance arising from the activity of integral membrane transporter proteins presents a global public health threat. In bacteria such as Escherichia coli, transporter proteins belonging to the major facilitator superfamily make a considerable contribution to multidrug resistance by catalysing efflux of myriad structurally and chemically different antimicrobial compounds. Despite their clinical relevance, questions pertaining to mechanistic details of how these promiscuous proteins function remain outstanding, and the role(s) played by individual amino acid residues in recognition, binding and subsequent transport of different antimicrobial substrates by multidrug efflux members of the major facilitator superfamily requires illumination. Using in silico homology modelling, molecular docking and mutagenesis studies in combination with substrate binding and transport assays, we identified several amino acid residues that play important roles in antimicrobial substrate recognition, binding and transport by Escherichia coli MdtM, a representative multidrug efflux protein of the major facilitator superfamily. Furthermore, our studies suggested that 'aromatic clamps' formed by tyrosine and phenylalanine residues located within the substrate binding pocket of MdtM may be important for antimicrobial substrate recognition and transport by the protein. Such 'clamps' may be a structurally and functionally important feature of all major facilitator multidrug efflux proteins.</p>

Formato

application/pdf

Identificador

http://pure.qub.ac.uk/portal/en/publications/insight-into-determinants-of-substrate-binding-and-transport-in-a-multidrug-efflux-protein(319c4a91-34cc-4659-8408-9762474f0366).html

http://dx.doi.org/10.1038/srep22833

http://pure.qub.ac.uk/ws/files/86034013/Inightsrep22833.pdf

Idioma(s)

eng

Direitos

info:eu-repo/semantics/openAccess

Fonte

Alegre , K O , Paul , S , Labarbuta , P & Law , C J 2016 , ' Insight into determinants of substrate binding and transport in a multidrug efflux protein ' Nature Scientific Reports , vol 6 , 22833 . DOI: 10.1038/srep22833

Tipo

article