Studies of Natural Extremophilic Enzymes

Proteins from extremophilic organisms, particularly thermophiles, have been the subject of intensive research in recent years. This work has been the subject of numerous reviews (Jaenicke and Bohm, 1998 Russel and Taylor, 1995 Vogt and Argos, 1997 Gerday et al., 1997 Somero, 1995), and we will make no attempt at an in-depth summary. We will confine ourselves to briefly stating the major trends identified thus far. Explaining these trends becomes complicated because the many weak interactions that determine enzyme stability and activity have complex temperature dependencies (see Section II). And evolution injects considerable confusion beyond the laws of physical chemistry. 

and weaker binding of ligands, including metals and other ions (Davail et al., 1994 Narinx et al., 1997 Aghajari et al., 1998 Kim et al., 

Comparisons of psychrophilic, mesophilic, and thermophilic enzymes suggest that a continuum of adjustments accompany adaptation to different temperatures (Davail et al., 1994 Feller and Gerday, 1997). Relative to mesophiles, the same kinds of weakly stabilizing interactions that are found in greater proportion in thermophilic enzymes appear in fewer numbers in their psychrophilic counterparts. 

The argument previously outlined provides an appealing physiochemi-cal explanation for the stability and activity behavior of homologous enzymes adapted to different temperatures. However, one cannot interpret the behavior of a biological system solely in physiochemical terms. All these enzymes are the products of evolution. While they are certainly subject to the laws of physics and chemistry, the evolutionary process imposes its own, additional constraints. We will see that the stability-activity trade-off is not a necessary characteristic of enzymes, especially not those evolved in the laboratory. 

Neutral mutations are neutral with respect to fitness. This does not mean they are neutral with respect to all enzyme behaviors. In fact, many neutral mutations will be deleterious to stability, catalytic ability, or any other property that does not contribute directly to fitness. Properties not protected by the purifying effects of natural selection can change as mutations accumulate, but the process is random and contains litde information that can be used to elucidate mechanisms (Benner and Ellington, 1990 Benner, 1989). 

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