The era where we see the
decline of antibiotics efficacy is approaching. To tackle the problem of fast
increasing antibiotic resistance, one approach is to target enzymes
that are involved in essential processes for the survival of bacteria. MraY,
the protein that is involved in cell wall synthesis has therefore been
identified as a drug-opportunistic target.
What has been done so far?
It is very challenging
to purify integral membrane proteins and overexpressing them for structural
study. However, the work that Chung and his co-workers has achieved was a
landmark event. They managed to crystallise MraY at 3.3 Å resolution and
solved the protein structure, which is consistent with previous topological
studies.
There has
still work to be done to understand the catalytic mechanism of MraY , but
the availability of the crystal structure facilitates these studies and will lead to the development of more targeted inhibitors. Inhibitors of MraY which are already being produced are: phloxine B which binds to the Mg 2+cofactor in the active site and michellamine B which binds to the hydrophobic groove present between TM5 and TM9 (Mihalyi et al., 2014). Both inhibitors compromising the catalytic activity of the enzyme and thus preventing the formation of peptidoglycan, leaving the bacteria prone to osmotic imbalance and cell lysis.
Really well-illustrated and relevant PyMol figures and animations. The explanations under "Introduction" and "Structure Determination" can be more concise but is engaging and flowing. Good mention of current work that builds on findings of Chung et al. that shows originality and reflection on direction of future research.
ReplyDeleteWell-presented blog! All the Pymol images are nicely done with clear labels. The videos showing the key residues in the active site of Mra Y are useful and relevant. The summary quiz at the end serves a good purpose on testing the understanding of reader upon finished reading your blog. Great work!
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