Biocurious

/ a biophysics blog

Molecule of the Month: Multidrug Resistance Transporters

Posted 1 November 2007 by PhilipJ under

Ever since the discovery of penicillin, we have lived our lives with far less fear of infectious disease. In the decades since then, a wide variety of drugs have been isolated from natural sources or synthesized by chemists, giving our doctors a large arsenal of antibiotics to fight infection. Bacteria, however, are dynamic evolving organisms, and they have developed many methods to fight back. In some cases, they develop ways to destroy antibiotic drugs directly, for instance, some bacteria make beta-lactamase enzymes that break down penicillin. In other cases, the bacteria change their own molecular machinery, making it invulnerable to the drugs. For instance, methicillin-resistant Staphylococcus bacteria use new, resistant enzymes to build their cell walls. If these methods don’t work, bacteria also have a more general method. They build special pumps that transport many different antibiotics out of the cell before they can do their job.

Multidrug resistance transporters find drugs that trying to gain entry through a cell membrane and they transport them back outside. The one shown here, Sav1866 from PDB entry 2onj, is found in Staphylococcus bacteria. The protein is composed of two identical subunits with a tunnel in between. Drugs enter the tunnel, and then cleavage of ATP in the large portion at the bottom causes a scissoring motion, opening the tunnel on the outer side and releasing the drug. This structure captures the protein in this final state, ready to release drugs upwards towards the outside of the cell membrane.

Read the rest from David Goodsell, here.

  

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