Malate dehydrogenase active site structure

FIGURE 20,20 (a) The structure of malate dehydrogenase, (b) The active site of malate dehydrogenase. Malate is shown in red NAD" is blue. 

A key structural and mechanistic feature of lactate and malate dehydrogenases is the active site loop, residues 98-110 of the lactate enzyme, which was seen in the crystal structure to close over the reagents in the ternary complex.49,50 The loop has two functions it carries Arg-109, which helps to stabilize the transition state during hydride transfer and contacts around 101-103 are the main determinants of specificity. Tryptophan residues were placed in various parts of lactate dehydrogenase to monitor conformational changes during catalysis.54,59,60 Loop closure is the slowest of the motions. 

Figure 9.8. The malate dehydrogenase dimer, indicating the location of the active sites in each protein plus the dimer interface. Malate dehydrogenase demonstrates substrate inhibition that has been attributed to subunit interactions and allosteric regulation by citrate, although the crystal structure of the protein reveals the absence of a separate allosteric site for citrate. See color insert.

The active site of lactate dehydrogenase could be redesigned to convert it to a malate dehydrogenase. (It was already known that the tertiary structures of the two enzymes were similar.) To take account of the increased... 

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