Chapter 3 (part 2) – Protein
Function
Test Your Knowledge
• (True/False) All proteins bind to other molecules. Explain.
• What sort chemical interactions create the “binding” between the
ligand and its protein partner? Name at least two.
• (True/False) A ligand binding site can be kept dry from
surrounding water molecules. Explain.
• Explain two different ways (structural) that proteins typically bind
to other proteins.
• What is Km? What does having a low Km say about the binding
between a protein and its ligand?
• What are some of the major functions of proteins in a cell? Name
at least 3 “categories”.
Protein-Protein Binding
Three major mechanisms:
• “surface string” interaction –
• “helix-helix” or “coiled coil” interaction –
• “surface-surface” interaction –
SH2 domain (example of surface string
interaction)
Central antiparallel bsheet surrounded by two
alpha helices
Coiled coil regions of Rad50
molecules bind together to form a
complex of molecules that help
repair DNA
Surface-to-surface
interaction between trypsin
and trypsin inhibitor protein
Protein-Ligand Interactions
Protein Binding Sites –Sterically and chemically “fit” the ligand;
Examples are antibodies and enzymes
• Water is typically excluded
from the binding site, but is
important to overall structure.
Why?
• Clustering of polar amino acid side chains can alter their
reactivity and increase the attraction of the ligand for the
binding site
cAMP bound to a binding site on a
protein
• Enzymes and bound ligand go through a number of
intermediate forms of different geometry. They are all
called transition states.
• The energy that it takes to get to the most unstable
transition state is called the activation energy.
• Enzymes speed reactions by selectively stabilizing the
transition state (ES) and actually have a much higher affinity
for the ligand in its transition state than the stable form of
the ligand.
• Enzymes not only bind to the substrate, but the nature of the amino
acids and their side chains within the binding site alter chemical
bonds in the substrate.
• Many enzymes can perform both acid and base catalysis because of
the different side chains in their binding site. This allows increased
speed of catalysis.
Many Enzymes Require Tightly Bound Small
Molecules to Function
• Enzymes sometimes form complexes that also improve efficiency
of reactions that may otherwise be diffusion-limited.
•Examples – pyruvate dehydrogenase, tryptophan synthase,
aminoacyl t-RNA synthetase