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3D mRNA
Function
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Single stranded
Internal base paring and loop formation
Termination of protein synthesis
Balances of multi protein units
pre-mRNA
• The first (primary) transcript from a protein
coding gene
• contains both introns and exons
• Pre-mRNA requires splicing (removal) of
introns
• the final mRNA molecule containing only
exons.
3D structure
of intron 3 in human cytochrome P450 2D6
structure
• The 5' end of the intron is located at the
top right part (white) G
• The 3' end is located on the left of the
figure (purple) G
secondary structure
• The intron is colored blue in the secondary
structure.
• The light red segments corresponds to the
exonic subsequences.
• The 5' end of intron 3 is labeled "GU“
• The 3 ' end is labeled "AG".
mRNA
Secondary structure
Hairpin structure
Hairpin structure
Antibiotic resistance
Bacteria are quick to fight back
• Bacteria reproduce very quickly, so bacterial evolution
is very fast.
• Some change the drug-binding proteins in subtle
ways, so that they still perform their function but do not
bind to the drugs.
• Some develop more effective ways to shield the
sensitive enzymes from the drug or methods to pump
drugs quickly away from the cell.
• The most common method is to create a special
enzyme, (for example: a beta-lactamase) that seeks
out the drug and destroys it.
Example: Penicillin-binding
Proteins
• The penicillin-binding proteins, (PDB entry
3pte), use a serine amino acid in their
reaction, colored purple here. The serine
forms a covalent bond with a
peptidoglycan chain, then releases it as it
forms the crosslink with another part of the
peptidoglycan network. Penicillin binds to
this serine but does not release it, thus
permanently blocking the active site.
• Other beta-lactamases do the same thing,
but use a zinc ion instead of a serine
amino acid to inactivate the penicillin.
• Many beta-lactamases use the same
machinery as used by the penicillinbinding proteins--so similar, in fact, than
many researchers believe that the betalactamases were actually developed by
evolutionary modification of penicillinbinding proteins.
Prions – protein nature
disease?
• How do the prions replicate?
• How do they course different diseases
within one species ?
• Prion protein was not modified in vitro.
• Different area of brain is affected like in
viral diseases.
• Heat and chemicals do not inhibit the
infectivity…..
Nature of science
• The protein-only hypothesis breaks new
conceptual ground.
• Those who have worked in this field under
other paradigms (like the virus or virino
hypotheses) are reluctant to accept this
new paradigm.
Nature of science
• Scientists from other fields are more
receptive to this hypothesis (broad
support).
• This hypothesis best explains all of the
observations about these agents and the
diseases they cause.
• If it fails to do so, the hypothesis will need
to be revised or rejected in favor of a
better hypothesis. That is the nature of
science