Assignment:

You are assigned the task of writing a web-based term paper that focusses on one of the six major classification of enzymes. Each of you will be assigned one of the six classifications to work with. These classifications include:

• Oxidoreductases
• Transferases
• Hydrolases
• Lyases
• Isomerases
• Ligases

Your termpaper should include a review of the general features of the reaction carried out by members of your classification. It should then focus on three specific examples that are chosen to illustrate the diversity of structures and strategies that have evolved to catalyze reactions with this classification. To this end, you should look for examples that

• Are not homologous, i.e., they do not share a common ancestor. If two proteins allign with less than 20% sequence identity they are usually considered non-homologous. You can use SwissPDBViewer or the ALIGN program to allign sequences and look for homologies.
• Have different folding topologies. Their classifications in the CATH and SCOP databases can be used to establish folding topologies.
• Involve different cofactors and amino acid groups in their active sites.

With your examples you should compare and contrast structure and function. The questions you address for each of your examples should include:

• How does the folding topology form the active site?
• What details are known about the catlytic mechanism?
• How varied are the reactions that are carried out using a specific mechanism?
• What are the thermodynamic considerations that need to be dealt with?
• What is the cellular location(s) of the enzyme?
• What cellular process(es) is the enzyme involved in?

When discussing structure and function, you should illustrate your web term paper with interactive three-dimensional molecular models using Jmol images. This will also allow you to embed buttons, that when pushed, will modify these images to illustrate points that you make in the narrative of your term paper. By using a web-based format for your termpaper, we will be able to publish your efforts for world-wide consumption. Please keep in mind, the content of your paper will be the primary factor used to evaluate.

Resources:

• The Protein Data Bank (PDB)
• The Narated tutorial

Your paper should draw from between 7 to 10 references. These should be references to scientific articles, not web sites. You can start by looking in the PDB files for the references to the articles in which the structure was reported. You should also use Literature dabases, such as PubMed and Science Citation Index, to expand your bibliography. Like the example structures, you should start with a large bibliography that you trim down as you polish you termpaper. You will be asked to submit copies of the articles that you reference along with your web site. Resources for developing a set of references include:

• The NIH's National Center for Biotechnology Information (NCBI) provides free online access to PubMed which you can use to do a key word search of the scientific literature.

• The Science & Engineering subject guide listing at the McIntyre library web page provides links to the full text of The American Chemical Society Journals, which includes Biochemistry, and the index BIOSIS.

• Science Citation Index: This extremely useful research tool allows you to find scientific articles which have cited a particular article of interest. For example, the PDB file for a protein provides the reference for the article in which a structure was first reported in the literature. You can use that citation in a Science Citation Index search to find other articles that refer to this article.

• Journal Web Sites
  • PubMed
  • Science Citation Index
  • Biochemistry (full text available online and at McIntyre)
  • Biophysical Journal (full text available online)
  • Nature (full text available online and at McIntyre)
  • Nature, Structural and Molecular Biology (full text available online)
  • Journal of Biological Chemistry (full text available online and at McIntyre)
  • Journal of Molecular Biology (abstracts online and full text available at McIntyre)
  • PNAS (Proceedings of the National Academy of Science, USA) (fultext available online or in McIntyre)
  • Proteins: Structure, Function, and Genetics (abstracts online, order articles through Interlibrary Loan )
  • Protein Science (full text available online)
  • Structure
  • Science Magazine (full text available online and at McIntyre)
  • Stryer's Biochemistry, 5^th Ed.
• Other Related Sites
  • NCBI (National Center for Biotechnology Information)
  • • Protein (Search for Protein Sequences)
  • EBI (European Bioinformatics Institute)
    • EMBOSS (Pairwise sequence alignment)
    • ClustalW (Multiple Sequence alignment)
  • ExPASy (Expert Protein Analysis System, Swiss Institute of Bioinformatics)
    • ENZYME (Enzyme nomenclature database)
  • CATH (Class, Architecture, Topology, Homology - Protein Structural Classification)
  • SCOP (Structural Classification of Proteins)
  • ALIGN (Pairwise sequence alignment)

Due Dates

• Wednesday, 23. November, 2005 - Submit a rough draft of the narrative for you site as a Word document.
• Wednesday, 7. December, 2005 - Submit your completed web site along with copies of the articles you referenced in your web site.

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[Chemistry Dept.] [Chem 406]

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Warren Gallagher
Department of Chemistry
(715) 836-5388
wgallagh@uwec.edu