The Enzyme Group

In 1969 at a meeting of the officials of the Science Research Council (SRC) the chemists present made a complaint that they were under-funded especially for major, expensive, modern pieces of equipment. The response they received from physicists was to the effect that if indeed there was a demand then it had to be demonstrated and given the costs of equipment any application for a grant would have to be made by a large group of researchers. E.R.H. Jones from the Dyson Perrins Laboratory, who attended the meeting, promised the committee that he would look into possibilities. On his return to Oxford he approached 

Knowles enquiring as to needs for costly equipment in chemistry. In turn Knowles put the question to his college colleague, R.J.P. Williams, who had been working for some three years on protein nuclear magnetic resonance using the somewhat unsatisfactory Varian 220 MHz NMR carrier wave spectrometer (not a Fourier transform instrument) based, very inconveniently, for a while at Harwell and then at ICI near Runcorn. (This work developed 

If we included the researches in the Enzyme Group many based on NMR and the achievements in Crystallography as well as the developments of other techniques described above as being in Physical Chemistry it is clear that it had an extremely fine record of achievement in these years in addition to those mentioned above. It is probably fair to state that at the end of this period, 1980, the department that had been the first to be of world-class, organic, was now the least impressive of the three. 

The changes in the Oxford Chemistry School were not as considerable in this period as they were between 1950 and 1980 when the major basic features of chemistry had been uncovered by a worldwide elfort. We shall see that the three Oxford Chemistry Departments often came to investigate dilferent aspects of these features, while other related departments, for example biochemistry and material science, viewed them with a somewhat dilferent emphasis. It is probable that chemistry itself had become a subject in which principles had been established but that many ramifications remained to be 

We start the description of each laboratory by reference to the holders of the chairs beginning with the Dr Lee s Professor of Physical Chemistry. As we have seen after Sir Rex Richards resigned to become the Warden (head) of Merton College in 1970 and subsequently Vice-Chancellor of the University, 1977-1981, Sir Frederick (later Lord) Dainton, who had been Vice-Chancellor of Nottingham University was elected (1970-1973). He was not able to accomplish much in his short stay. He was followed from 1974-93 by (Sir) 

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The last enzymatic step of the cannabinoid pathway is the production of THCA (3.5), CBDA (3.4) or CBGA (3.6). The compounds are produced by three different enzymes. The first enzyme produces the major psychoactive compound of cannabis, THCA [21,38] the second and third are responsible for the production of CBDA [39] and CBGA [40], respectively. All of these enzymes belong to the enzyme group oxidoreductases [38-41], which means that they are able to use an electron donor for the transfer of an electron to an acceptor. From these enzymes only the THCA and the CBDA synthase gene sequence have been elucidated. Their product also represents the highest constituent in most C. sativa strains. 

We may note, parenthetically, that a somewhat similar possibility exists for the enzyme group in which the cofactor is pyridoxal phosphate... 

Within the NiFe(Se) hydrogenase family, the unrooted tree (Fig. 2.4) clearly reveals several major lineages. As might be expected, the enzyme groups discussed above all emerge as distinct clades which reflect the major prokaryotic groups and the enzyme... 

The enzymes grouped in this section are biologically very distinct. Lip, by definition, catalyzes the hydrolysis of one or more of the three ester bonds linking fatty acids to the hydroxyl positions of glycerol (Equation (6)). 

The range of catalytic proficiencies for enzymes suggests that there are features of catalysis in enzymes that involve factors other than stabilization of transition states. One important distinction is that the enzyme active site contains catalytic groups that are able to access reactive intermediates, while intermediates formed in solution have lifetimes that are less than the time needed for a reagent to diffuse to the site of the reaction.33 In the enzyme, groups are initially associated with the bound substrate in a specific array and continue to be available through the course of the reaction. Diffusional introduction of catalytic groups is overcome by pre-association of the catalysts and reactant prior to the formation of any reactive intermediate. This accesses modes of catalysis that are not possible if the catalyst and intermediate must become associated after the intermediate has formed. 

Fig. 8-2 Binding of the substrate (NAG-NAM)3 to the active site of lysozyme. The substrate is drawn with bold bonds, the enzyme groups with light-face bonds. H bonds are indicated by dotted lines.

Fig. 19.20. Schematic drawing of hydrogen-bonding interactions between the enzyme tyrosyl-tRNA synthetase and the substrate analog tyrosyl adenylate. The enzyme groups interacting with tyrosyl adenylate are boxed, MC indicates main-chain C=0 or N-H groups [647]...

Kimura and his associates have been preeminent in exploiting the potential of Zn(II) complexes of pendant-arm polyaza macrocycles to act as models for the hydrolytic Zn(II)-containing enzymes. Collectively, their work in this area involves structurally unmodified macrocycles as well as pendant-arm macrocycles, and the reader is referred to a number of reviews 6-15) that summarize their work in its entirety. The particular object of this section is to examine how different types of pendant arm have been introduced onto a macrocyclic framework and how it has been possible to utilize their presence to elicit information of relevance to a particular group of enzymes. The enzyme groups studied using pendant-arm macrocycles have been the alkaline phosphatases and the class II aldolases. 

Damaging mechanisms work mainly in two directions, namely a) local affection of mucous membranes and skin in the contact areas, provoked by the new irritative-destructive effect products formed by the interaction between the poison and the water component of the mucous secretions (for methylizocyanite etc.) b) blocking of the enzyme groups in brain and other specialised cells, which conduct the intracellular oxidation (cytochromoxidase) etc. 

G.K. Radda, fellow/lecturer in Chemistry, but later in Biochemistry (1966), together with the direct study of mechanisms of organic reactions on the intake of other new fellow/lecturers. We must also observe that Knowles and W.J. Albery (1963), of physical chemistry, were tutorial pupils of R.P. (Ronnie) Bell and the three met frequently to discuss solution kinetics before Bell departed to Stirling in 1967. Knowles and Albery also had a very fruitful collaboration in work on mechanistic aspects of enzyme kinetics. Because the mechanistic work on enzymes was mostly conducted at least initially when Knowles was a member of the Enzyme Group, a cross-department body, it is better to describe the enzyme work under that heading. We therefore turn to traditional organic chemistry synthesis. 

The Enzyme Group. There is an account of it in the Bodleian Library Special Collections, Shelfmark MSS. Eng. 2662-81. d. 2251. 

The atherogenic capacity of HDL can be Umited via enrichment of the lipoprotein with the enzymes group llA secretory phospholipase A2 and myeloperoxidase, and other factors such as triglycerides, ceruloplasmin, serum amyloid A, and haptoglobin-hemoglobin complex [144,145]. 

Atom replacement exchanges one atom within an enzyme for a different atom. Such replacements can modify enzyme activity or change the substrate specificity of the enzyme. Group attachment involves the use of particular chemical reagents to attach particular molecules to enzymes. Attaching additional molecules to enzymes can also markedly change enzyme activity and substrate specificity. 

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