Organic structure determination reliability

By far the most reliable method to determine the absolute configuration of chiral inorganic and organic compounds is by single-crystal X-ray crystallographic analysis.4 By 1974 Saito listed 59 chiral metal complexes whose absolute stmctures were determined by X-ray diffraction.181 Advances in the speed of computer processing and other aspects of X-ray instrumentation have resulted in the ability to determine absolute structures from much smaller crystals. As a consequence, the number of crystal structure determinations of inorganic compounds has increased enormously in recent years. 

At the start of the twenty-first century, the pace of membrane protein structure determinations is clearly accelerating (Figure 1). With the exceptions of rhodopsin (Palczewski et al., 2000) and the calcium ATPase (Toyoshima et al., 2000), however, eukaryotic channels, transporters, and receptors are conspicuously absent from the list of known membrane protein structures. These two exceptions, as proteins of naturally high abundance, highlight the current reality that no structure has been determined for an overexpressed eukaryotic membrane protein. This situation reflects the present difficulties in the reliable overexpression of membrane proteins, particularly those of eukaryotic organisms. Just as the development 20 years ago of overexpression systems for water-soluble proteins revolutionized the structure determinations of this class of proteins, advances in membrane protein expression will be essential to successful realization of the goal of routine structural analysis of membrane proteins. 

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