17 Jul 2014

Utilizing the PDB and HSAB theory to understand metal specificity in trafficking proteins

In-Class Activity

Submitted by Erica Gunn, Simmons College

This is an in-class PDB exercise based on the paper "Mechanisms Controlling the Cellular Metal Economy" by Gilston and O'Halloran. Students are asked to visualize the metal binding sites of several proteins discussed in the paper, highlighting unusual metal geometries. After identifying the amino acid residues involved in metal binding, students will discuss the bond structure in terms of HSAB theory. 

Learning Goals: 
Students will:
1) Become familiar with reading primary literature and using referenced works.
2) Use the PDB to search for protein structures and create images of metal binding sites.
3) Apply coordination chemistry and HSAB to describe bonding in biological systems
4) Practice drawing chemical structures
Equipment needs: 

Laptop computers with Java installed for accessing the PDB (freely available at www.pdb.org). Instructions for using the PDB can be found in the related activities linked below.

Implementation Notes: 

Cys79 is a bridging ligand between Zn402 and Zn401 in ZntR. 

You can highlight two metal atoms in the PDB viewer by holding shift while clicking. 

It is a good idea to pre-test computers that will run the PDB viewer before coming to class, as the viewer runs on Java and may have technological issues. 


Evaluation Methods: 

This learning object was developed for the 2014 VIPEr workshop and has not been evaluated. 

Creative Commons License: 
Creative Commons Licence


I used this literature discussion in my second-year inorganic chemistry course as an applied example of the hard-soft acid base concept and as a way to introduce students to metal binding in proteins (as well as the PDB). In the section on HSAB, students accessed the PDB during a lecture period in order to visualize the bonding schemes presented in the paper, and we discussed the bonding preferences in terms of HSAB theory. In the last lecture of the semester, we returned to the content of the paper and Dr. O'Halloran's TED talk to discuss the important and varied roles that metals play in cell biology, as well as the exciting and truly multidisciplinary opportunities for research in this field. 
This topic was a great way to end the class. Students were fascinated by the zinc spark images presented in the TED talk, and were excited to see a direct application for several of the topics that we had covered in the course. One student remarked that she had studied the cell maturation and fertilization process in a previous biology class, but had never connected those ideas with the chemistry that was occurring inside the cell until seeing the TED video.
I corresponded with Dr. O'Halloran after this lecture, and he informed me that his group has just published a new paper on this topic, in Nature Chemistry in Dec 2014 (doi:10.1038/nchem.2133). This new paper would be a great way to extend and deepen the discussion of this topic in future courses. 

Thanks for the evaluation notes Erica! That comment by the student is golden! I am going to try to use this in class in spring quarter. 


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