Enzyme inhibitors, structure-function correlation

In a very broad overview of the structural categories one can state several statistical correlations with type of function. Hemes are almost always bound by helices, but never in parallel a//3 structures. Relatively complex enzymatic functions, especially those involving allosteric control, are occasionally antiparallel /3 but most often parallel a//3. Binding and receptor proteins are most often antiparallel /3, while the proteins that bind in those receptor sites (i.e., hormones, toxins, and enzyme inhibitors) are most apt to be small disulfide-rich structures. However, there are exceptions to all of the above generalizations (such as cytochrome cs as a nonhelical heme protein or citrate synthase as a helical enzyme), and when one focuses on the really significant level of detail within the active site then the correlation with overall tertiary structure disappears altogether. For almost all of the dozen identifiable groups of functionally similar proteins that are represented by at least two known protein structures, there are at least... 

The regions of residues 46-49 and of tyrosine 115 must be located in the section of the binding site which interacts with that part of the substrates or inhibitors extending to the 3 -carbon side of the basic structural element, R-dpT. This region is probably of importance in the binding function of the enzyme. More exact correlation of affinity labeling... 

Scoring of both conformations resulted in conclusion that the first one (A) is correct. Higher than that of conformation B affinity of the inhibitor results from additional strong interaction with Arg359 — similar to that found in glutamate-GS complex.95 In order to support that conclusion several other known inhibitors of GS were docked into the active site of the enzyme and scored with eight different functions. In all cases good correlation was found, which confirmed the correctness of the obtained structures and particularly the correctness of the conformation A of PPT in GS active site. 

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