Three-point attachment proposal, citrate

Ogston offered an explanation, called the three-point attachment proposal, that was to initiate the concept of prochirality. If citrate is represented as a three-dimensional structure (Fig. 12-12), then on the assumption that a three-point attachment to aconitase is necessary for catalysis, it is apparent that citrate can only be accommodated in one orientation. The removal of the elements of water can then only occur from one particular half of the symmetrical molecule. 

Early attempts to purify the enzyme brought the quick realization that aconitase is easily inactivated (6,7). In the early 1950 s Dickman and Qoutier (8,9) found that inactivated aconitase could be reactivated by incubation with iron and a reduc-tant. From kinetic analyses of the iron and reductant effects on enzyme activity, Morrison argued that both formed Michaelis-Menten complexes wiA the enzyme (10). This refuted the earlier idea that the sole role of the reductant was to maintain iron in a reduced state (9). Of several metal cations tried, only ferrous ion was found to be capable of this reactivation process (8,11). Because of the absolute requirement for iron in activation, the known chelation properties of citrate, and Ogston s 3-point attachment proposal, Speyer and Dickman proposed that the active site iron provides three coordination sites for substrate binding - one for hydroxyl and two for carboxyl groups (12). 

Ogston [20,21], seemingly unaware of the Easson-Stedman model, proposed a similar three-point attachment model to rationalize the observed stereoselectivity in the enzymatic transformation of symmetrical prochiral substrates, e.g., citrate and aminomalonate (Fig. 3) [22]. Similarly, Dalgleish [23], also unaware of the Easson-Stedman model [17], rationalized his observations concerning the resolution of the enantiomers of a number of amino acids on paper chromatography by a three-point attachment. In a subsequent telephone conversation with Bentley [24], Dalgleish stated that he was terribly impressed by the Ogston hypothesis. It is therefore... 

---