Problem Set #6: Proteins on the Web
Due October 28th at
the beginning of class
far we have used several tools on the web for exploring protein structure. This week I would like you to
synthesize what we have done before to compare two enzymes, triosephosphate
isomerase and dihydroorotate
dehydrogenase. These enzymes are some similarities but have differerent
functions. Examine these proteins
using the resources we have used in the first four problem sets to determine
how they are similar and different.
In particular, begin thinking about how the structure relates to
function: these are enzymes!
ways you might explore these proteins might be to
- use the PDB to find their
structures (human triosephosphate isomerase is 1hti.pdb; human
dihydroorotase is 1d3g.pdb).
Look at the headers and the pictures to find out some basic
information and see if they have overall similar structures.
- Download the files and use
Rasmol or SwissPDB Viewer to look at the structures. What kind of shape do these
proteins have, and how are they similar and different?
- Try to draw a topology
diagram. Based on the overall
shape and fold, do you see any reason to believe that these proteins may
- Look at their active
sites. Both of these proteins
are enzymes, which means that they catalyze chemical reactions. Where are the active sites, what
cofactors or side chains are involved in the catalysis, do their
substrates have any similarities in size, structure, etc.?
- How related are
triosephosphate isomerase and dihydroorotase? Use SCOP or CATH to determine whether these proteins
belong in the same class, family, or whatever. Do you think they may have evolved from a common ancestor
- Try to overlay the two
sequences and/or structures to accentuate their similarities and
differences. You may have to
play around with this for a while, because their sequence similarity is
low enough that most computer programs have a hard time finding the
similar parts. Places you
might try this: the fitting programs in SwissPDB Viewer (copies of the
manual are available); the sequence overlaying functions in the
NIH-Genebank site “Entrez” (you will have to look up the sequences first;
it will help you to know that human dihydroorotase is part of a larger
enzyme complex called CAD); the protein comparison web site DALI (http://www2.ebi.ac.uk/dali/); other sites on the
- Use the NIH-Genebank website
“Entrez” and/or ISI Web of Science to find out more about these proteins,
their functions, and their nearest structural/evolutionary neighbors.
you have compiled a bunch of information about these proteins, I would like you
to synthesize the information into a concise but informative presentation. An abstract (~1 typed page) plus
several figures with figure legends should suffice to get across the major
points. Some hand-drawn figures