Biological enzyme modeling active site structure

Enzymes are biological catalysts. They enhance reaction rates because they provide an alternative reaction pathway that requires less energy than an uncatalyzed reaction. In contrast to some inorganic catalysts, most enzymes catalyze reactions at mild temperatures. In addition, enzymes are specific to the types of reactions they catalyze. Each type of enzyme has a unique, intricately shaped binding surface called an active site. Substrate binds to the enzyme s active site, which is a small cleft or crevice in a large protein molecule. In the lock-and-key model of enzyme action, the structures of the enzyme s active site and the substrate transition state are complementary. In the induced-fit model, the protein molecule is assumed to be flexible. 

Metal-sulfur aggregates are now known to occur in biological systems as the active sites of a significant number of metalloenzymes, and clarification of their detailed structures are currently progressing rapidly. In consideration of the results of these studies, many researchers are attempting to synthesize the direct structural models as well as the functional models of the active sites of natural enzymes that promote various important reactions in the biological systems under ambient conditions, which presumably leads in the near future to the... 

A knowledge of the structure of the H2—activating site is not only important for an understanding of the mechanism of action of the enzyme but is relevant for practical applications since it may provide clues on how to improve on, e.g., 02—and pH-instability. From a different perspective the active site may be a model to be mimicked by the inorganic chemist thus altogether eliminating the biological aspects of the problem. 

Despite their potential importance, there are few analytical models of whole cell biosensing devices—particularly when compared to the plethora of models describing enzyme based biosensors [62]. Although aspects of cellular biochemistry are similar to those of isolated enzymes [63], problems arise in modelling the physicochemistry of whole cells due to their complex nature they are large (typically 0.2-10 jxm) they may contain a variety of biological structures (membranes, organelles, etc.) they incorporate a diversity of biochemical pathways and they may contain many types of active site. 

Flavin-dependent le -transfer in enzymes and chemical model systems can he differentiated from 2e -transfer activities, i.e., (de)hydrogenation and oxygen activation, by chemical structure and dynamics. For le -transfer, two types of contacts are discussed, namely outer sphere for interflavin and flavin-heme and inner sphere for flavinr-fenedoxin contacts. Flavin is the indispensable mediator between 2e - and le -transfer in all biological redox chains, and there is a minimal requirement of three cooperating redox-active sites for this activity. The switch between 2e - and le -transfer is caused by apoprotein-dependent prototropy between flavin positions N(l)/0(2a) and N(5) or by N(5)-metal contact. 

The majority of cyanide-bridged dinuclear complexes described for the combination of metal ions belong to the biologically relevant class of Cu —Fe dimers. These compounds serve as models for the binuclear cyanide-inhibited site of cytochrome c oxidase, an enzyme that contains the heme-copper active site responsible for the O2 reduction chemistry (59). The lethal toxicity of cyanide was traced to its irreversible binding and inhibition of this active site in the enzyme (60). The biologically relevant aspects of these complexes were the subject of many reports (61,62). Our interest is in describing their crystal structure, which will be correlated to the magnetic properties in a later section. 

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