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PDB 1XR6 Christian Tyler Marcum Medicinal Chemistry – Dr. Benjamin Clayton

The Crystal Structure of the RNA Polymerase from the Human Rhinovirus

Human rhinoviruses (Fig. 1) are the viral agents responsible for the common cold and flu-like symptoms in humans. This structure is an x-ray crystallography of the RNA Polymerase from the human rhinovirus accurate to 2.5 angstroms. Its polymerase function is key to the continuation of the viral RNA and, therefore, the rhinovirus itself. As one can surmise, the polymerase is key in the reproduction of the viral RNA (therefore the virus itself) and thus is a target for many new anti-viral agents. Its dimensions are 88.39, 88.39, and 186.20 angstroms. The structure of the polymerase can best be described as a hollow ring of alpha-helixes toward the back of the molecule, with a concurrent ring of beta-pleated sheets toward the forefront (Fig 2.). The molecule constitutes seventeen alpha helixes of varying sizes as well as nine beta-pleated sheets arranged all but once in anti-parallel fashion stacked against one another. The active site is most likely the hollow section in the middle by which it can bind to the RNA strands, though it is also suggested that anti-viral agents are likely to look for an alternative binding site as to avoid mimicking RNA. My suggestion for an alternative binding site would be at (Fig. 3, Site B). It happens to contain convenient binding groups as well as a nearby source for Van der Wall’s interactions in the form of a ring.


Figure 1.

Figure 2.


Figure 3.

Site B

Med Chem