44 M. H. Akabas
4 Conclusions
Cysteine substitution mutagenesis has been a powerful approach for studies of the
structure and function of a wide variety of ion channels and other membrane pro-
teins. The reactivity of cysteine has made it a useful target for site specific chemical
modification. The development of a diverse group of sulfhydryl reactive chemi-
cals has provided the reagents to probe the accessibility of the substituted cysteines
to modification or the use of engineered cysteines for site specific labeling with
fluorescent or paramagnetic probes as are discussed in other chapters of this book.
Although the resolution of SCAM studies does not approach that of x-ray crys-
tallography, its power is derived from the fact that it allows studies of functional
proteins embedded in their native lipid membrane environment. Thus, information
derived from SCAM studies and site specific cysteine labeling studies can help to
validate the conclusions drawn from x-ray crystal structures of ion channels where
the functional state of the protein that has crystallized is often ambiguous.
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