#12 Stereospecific Properties

It was the French biochemists François Jacob and Jacques Monod working in the 1960s who recognized the significance of the shape-recognition properties of protein enzymes with their substrates, and protein transcription factors with DNA.

Morphogenesis is microscopic.  Monod anticipated that,

“…. the construction of a tissue or the differentiation of an organ – macroscopic phenomena – must be viewed as integrated results of multiple microscopic interactions due to proteins, and as deriving from the stereospecific recognition properties of those proteins, by way of the spontaneous forming of noncovalent complexes.” (Monod 1970, page 88).

The fundamental principle of associative stereospecificity accounts for the discriminative properties of proteins (Monod, 1970, page 104).  It also accounts for the complementarity of the DNA strands which allows replication to occur.  “In a very real sense it is at this level of chemical organization that the secret of life (if there is one) is to be found.” (Monod 1970, page 94).

Monod writes that proteins have complex foldings that determine the molecule’s three-dimensional structure, including the exact shape of the stereospecific binding sites by which the molecule performs its recognition activity.  It is the sum of the noncovalent interactions that stabilizes the functional structure of the protein.  It interacts through noncovalent bonds with other molecules.  The precision of structure of proteins encoded in the amino acid sequence is indispensable to their specific binding properties (Monod 1970, page 90-91).

It emerges that two things are very important to the functioning of the genetic system: firstly that subunits associate in predictable ways as units (rather than amorphous masses that disintegrate), and secondly that the subunits are associated by noncovalent bonds that can be broken by relatively mild treatment.

For example, the noncovalent hydrogen bonds between complementary base pairs can be broken and the two DNA strands unzipped for replication to occur without the covalent bonds holding the DNA backbone together in each strand being affected.

Another more recently investigated example is that the mediator (or molecular bridge) involved in the transcription of DNA has 20 subunits united by noncovalent bonds whose energy equals one covalent bond.  This is possibly just enough force to allow the DNA to be released from one covalently bonded methyl group so that transcription can occur.  The weakness in the bonds between the mediator subunits also allows them to disassemble when transcription is completed (Allison 2007, pages 336, 337, 340).

It is important to understand that organic ingredients act as units of complex molecules that do not combine in a random fashion, but according to their chemical preferences for bond formation.  The units have some properties of self-assembly and spontaneous association.  Properties of self-assembly are not to be confused with stereospecificity.  Monod (1970, pages 104-105) points out that the DNA structure can accommodate any sequence of DNA bases.  The sequence of DNA bases is entirely ‘free’; it is not determined by chemistry.  This is what makes DNA an information carrier.  The DNA sequence specifies the stereospecific properties of the protein products.

The structure of DNA is achieved by complementary base pairing.  The nucleotide bases A and G are purines which means that they are composed of two fused rings.  The nucleotide bases C and T are pyramidines which means they only have one ring.  Base pairing occurs such that A and T form two hydrogen bonds with each other, while C and G form three hydrogen bonds with each other.  Thus, in double helix DNA where there is A in one strand there is T in the other, and where there is C in one strand there is G in the other.  The two strands of DNA are complementary to each other.  The pairing of nucleotide bases is stereospecific – it is always the same, but the order of nucleotide bases along the DNA strands is entirely free and not dictated by bonding properties.  The structure of genes is therefore not stereospecific.

Monod (1970, pages 78-79) calls this the concept of gratuity –that the function of allosteric enzymes is not determined by chemistry.  The specificity of the interactions is due to the structure of the protein in the various states it is able to adopt, a structure freely and arbitrarily dictated by the structure of a gene.

“An allosteric protein should be seen as a specialized product of molecular ‘engineering’, enabling an interaction, positive or negative, to take place between compounds without chemical affinity, and thereby eventually subordinating any reaction to the intervention of compounds that are chemically foreign and indifferent to this reaction.” (Monod 1970, pages 78-79).

We may conclude that the functioning of the living cell is not determined by the laws of chemistry.  Life transcends the laws of chemistry and the laws of physics.  Chemistry, and especially the properties of different types of bonds do, however, impose some order on the genetic system.  No system would continue to function without various levels of order.

In the minds of some people, the discovery of levels of order that may be produced by the spontaneous association of organic molecules is interpreted as meaning that there need be no rational intention or design behind nature.  They believe that nature functions according to laws naturally and spontaneously with no other input being necessary.  Some people have confused the stereospecificity of protein enzymes and the nucleotide structure of DNA with the totally free ordering of nucleotide bases in the structure of genes; they believe that genes are specified by natural rules of assembly.  Thus, they have not understood that although information is carried by an ordered molecule called DNA, the information DNA carries has another source.