As many of the structural genomics centers have ended their first phase of operation, it is a good point to evaluate the scientific impact of this endeavour. The Structural Genomics Consortium (SGC), operating from three centers across the Atlantic, investigates human proteins involved in disease processes and proteins from Plasmodium falciparum and related organisms. We present here some of the scientific output of the Oxford node of the SGC, where the target areas include protein kinases, phosphatases, oxidoreductases and other metabolic enzymes, as well as signal transduction proteins. The SGC ?tul?> has aimed to achieve extensive coverage of human gene families with a focus on protein-ligand interactions. The methods employed for effective protein expression, crystallization and structure determination by X-ray crystallography are summarized. In addition to the cumulative impact of accelerated delivery of protein structures, we demonstrate how family coverage, generic screening methodology, and the availability of abundant purified protein samples, allow a level of discovery that is difficult to achieve otherwise. The contribution of NMR to structure determination and protein characterization is discussed. To make this information available to a wide scientific audience, a new tool for disseminating annotated structural information was created that also represents an interactive platform allowing for a continuous update of the annotation by the scientific community.

processesCarbonyl reduction is a significant step in the biotransformation leading to the elimination, of endogenous and exogenous aldehydes, ketones and quinones. This reaction is mediated by members of the aldoketo reductase and short-chain dehydrogenaseheductase (SDR) superfamilies. The essential role of these enzymes in protecting organisms from damage by the accumulation of toxic carbonyl compounds is generally accepted, although their physiological roles are not always clear. Recently, the SDR enzyme 1 1P-hydroxysteroid dehydrogenase-I has been identified to perform an important role in the detoxification of non-steroidal carbonyl compounds, in addition to metabolising its physiological glucocorticoid substrates. This review summarises the current knowledge of type-1 1 1P-hydroxysteroid dehydrogenase and discusses possible substratehnhibitor interactions. They might impair either the physiological function of glucocorticoids or the detoxification of non-steroid carbonyl compounds.Keywords: aldehyde ; ketone and quinone detoxification ; nicotine-derived nitrosamine ketone, carbonyl reduction; reductive metabolism; 1 I@-hydroxysteroid dehydrogenase ; short-chain dehydrogenasekeductase ; steroid metabolism ; microsomal reductase ; xenobiotic metabolism.Over the last decade 1 lp-hydroxysteroid dehydrogenases (1 1P-HSD) have received increasing attention from the scientific community. These enzymes have a multitude of (patho)physiological functions and a wide tissue distribution of isoforms. The key role of their enzymatic activity is the metabolism of physiologically occurring glucocorticoids, i.e. the 1 1P-oxidoreduction of cortisol (corticosterone) and cortisone (dehydrocorticosterone).However, in 1993 it was discovered that hepatic 11P-HSD-1, in addition to its role in the metabolism of physiological steroid substrates, is also capable of catalysing the carbonyl reduction of non-steroid xenobiotic aldehydes, ketones and quinones [ 1,