CHAPTER 5:  BINDING

Biochemistry Online:  An Approach Based on Chemical Logic

08/08/2002

We have finished studying protein structure. Now we want to consider what proteins do. The first thing any macromolecule must do in order to effect some function is to bind a ligand. Hence we will initiate our studies of protein function by looking the most studied proteins, myoglobin and hemoglobin, which bind a simple ligand, dioxygen. We will then study how specific proteins bind the very large "ligand" DNA. Finally we will look at the binding of drugs to macromolecules and the future of drug development.

The links below will take you to a description of many of the handouts I have distributed in class. This online guide is meant to augment your understanding of what we have discussed in class, and not a replacement for class attendance.

  1. Reversible Binding I: Equations and Curves
  2. Reversible Binding II: Experimental Binding Curves, Kd, and Error Analysis
  3. A Model Binding System: Myoglobin. Hemoglobin, and Dioxygen
  4. Binding and the Control of Gene Transcription 
  5. New Methods in Drug Development

Recent References

  1. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors.  (Rheumatoid factor)  Leadbetter et al., Nature. 416, pg 595, 603, (2002)
  2. Mouse urinary proteins, bind and release small volatile odorants; Highly polymorphic proteins.  Used to differentiate individuals in social behavior.  Nature:  414, pg 590 and 631 (2001)
  3. Fritz et al. Translating Biomolecular Recognition into Nanomechanics.  Science. pg 316 (2000)
  4. Grakoui et al. The Immunological Synapse:  A molecular machine controlling T Cell Activation Science. 285, pg 207, 221 (1999)
  5. Guo, Zhou, and Schultz.  About small ligand that regulate interactions between proteins.  Science. 288, pg 2042 (2000)
  6. DeLano et al. Converget solutions to binding at a protein-protein interface.  (a protein can bind many other proteiins through similar set of contact residues - cross-reactive binding.  What promotes this?)  Science. 287, pg 1279 (2000)
  7. Kobe and Kemp.  Active Site directed protein regulation (intrasteric regulation of active site, the counterpart of allosteric control)  Nature. 402, pg 373 (1999)
  8. Uetz et al. Guilt by Association.  (about 2 hybrid analysis of protein-protein interactions in yeast.  good graphic).  Nature. 403, pg 601 (2000)
  9. Lynch et al. Characterization of the human cysteinyl leukotriene (derivative of arachidonic acid) CysLT1 receptor.  Nature. 399, pg 789 (1999)
  10. Gavin et al., Ho et al. Protein Complexes take the bait (about probing protein-protein interactions in the proteome - using  newly described bait proteins and mass spec. to probe multiprotein complexes - more than dimers)  Nature. pg 123, 141, 180 (2002)

  11. Di Cera, E. Site-Specific Thermodynamics: Understanding Cooperativity in Molecular Recognition.  Chem.  Rev. 98, 1563-1591(1998)

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