Anesthesia Pharmacology Chapter 4:  Physics and Anesthesiology

Globular Proteins

• Although we have just spent some time discussing fibrous proteins, many of the most interesting proteins are nonstructural but rather have specialized functional properties. 

  • Specific functions include proteins as mediators of transport, as catalysts (enzymes), hormones, i.e. peptide hormones and immunoglobulins. 

  • These proteins tend to be globular rather than fibrous and have more  complex secondary structures.  The tertiary structure of a protein is based on the relationship between secondary structures previously identified, i.e. alpha & beta helices.

• As the protein's primary structural sequences defined implicitly by the nucleotide DNA sequences, the ultimate function of the globular protein is manifest at the quaternary and tertiary structural levels. 

  • In other words, the sequence of amino acids by themselves wouldn't do anything until a highly regulated process of folding occurs dictated by the sequence and in accord with thermodynamically favored structures.

• Much like our consideration of very small molecules, much larger protein molecules should not be regarded as static structures but rather a structures that exhibit internal motions exploring various configurations or confirmations.

  • Furthermore, some proteins such as drug receptors have specific regions called binding domains which interact with some specificity with small molecules. 

    • The interaction itself between the small molecule in the proteins binding domain may induce conformational changes that in turn change protein function. 

    • What we have examined earlier with respect to oxygen binding to hemoglobin affected by protons binding to special sites in influencing the oxygen-hemoglobin dissociation curve is analogous to the effect of benzodiazepines such as diazepam (Valium) on the chloride conductance property of GABA receptors.

• To summarize our discussion of proteins in the components that yield higher-order structure we have:

  1. amino acid linear sequences

  2. alpha helices (beta sheets, turns etc.)

  3. polypeptide chains (for example tropocollagen or mixtures of alpha & beta helices)

  4. oligomeric proteins consisting of subunits, such as hemoglobin, nicotinic cholinergic receptors and many other receptor systems.

 

• ⁵⁴Lehninger, AL, Nelson, DL, Cox, MM, "The Three-Dimensional Structure of Proteins" in Principles of Biochemistry with an Extended Discussion of Oxygen-Binding Proteins, Chapter 7, , 160-187,  Worth Publishers, New York, 1993.