Glutathione S‐transferases (GSTs) are a family of enzymes involved in the cellular detoxification of xenotoxins. Cytosolic GSTs have been grouped into four evolutionary classes for which there are representative crystal structures of three of them. Here we report the first crystal structure of a theta‐class GST. So far, all available GST crystal structures suggest that a strictly conserved tyrosine near the N‐terminus plays a critical role in the reaction mechanism and such a role has been convincingly demonstrated by site‐directed mutagenesis. Surprisingly, the equivalent residue in the theta‐class structure is not in the active site, but its role appears to have been replaced by either a nearby serine or by another tyrosine residue located in the C‐terminal domain of the enzyme.

Letter to the Editor this criteria correspond to known functional groups of A Unified Nomenclature System for receptors. This procedure yields six subfamilies. All the the Nuclear Receptor Superfamily unusual receptors that contain only one of the two conserved domains (C or E) were grouped into a separate subfamily (subfamily 0) irrespective of their evolutionary Nuclear hormone receptors (NRs) are important tranorigin. Within subfamilies, groups of receptors are descriptional regulators involved in widely diverse physiofined as the most internal branches with bootstrap vallogical functions such as control of embryonic developues above 90%. In this nomenclature system, the numment, cell differentiation, and homeostasis (Gronemeyer ber of a given receptor inside a group does not carry and Laudet, 1995; Mangelsdorf et al., 1995). In addition, any specific information. In many cases these groups these molecules are extremely important in medical recontain arthropod and vertebrate members. The various search since a large number of them are implicated in homologs of the same gene in invertebrates (e.g., Drodiseases such as cancer, diabetes, or hormone resissophila and Caenorhabditis) have the same name. It is tance syndromes. Some of the NRs act as ligand-inducible transcription factors, while a large number of them have no defined ligand and are hence described as "orphan" receptors (Enmark and Gustafsson, 1996). Over the last decade, workers in the field have described more than 300 sequences of NRs using an increasingly complex and baroque nomenclature. The existence of several names for the same gene is an acute problem for the orphan receptors, which often cannot be described by their function, particularly at the moment of their discovery. As discussed during the Seventh International CBT Symposium on "Nuclear Orphan Receptors" in Huddinge, Sweden (September 9-12, 1995), this plethora of names has become more and more confusing and now constitutes a barrier for understanding of newly acquired knowledge to researchers outside as well as within the field. For that reason, four of us (V. L., J. A., J.-A. G., and W. W.) agreed to form a committee for the nomenclature of NRs. It is the purpose of this paper to recommend names for the subfamilies and groups of receptors based on a phylogenetic tree connecting all known NR sequences. This system, based on the evolution of the two well-conserved domains of NRs (the DNA-binding C domain and the ligand-binding E domain), offers a practical and significant framework to which subsequent genes can be easily added. The resulting nomenclature has now been endorsed by over 40 scientists 1 many of whom contributed to defining the nomenclature and to preparing this letter. This nomenclature has been discussed with the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR). A subcommittee of NC-IUPHAR entitled "Nuclear Receptors" will be set up to further clarify receptor nomenclature to integrate structure and function.A summa...

The neuraminidase inhibitors zanamivir and oseltamivir are marketed for the treatment and prophylaxis of influenza and have been stockpiled by many countries for use in a pandemic. Although recent surveillance has identified a striking increase in the frequency of oseltamivir-resistant seasonal influenza A (H1N1) viruses in Europe, the United States, Oceania, and South Africa, to date there have been no reports of significant zanamivir resistance among influenza A (H1N1) viruses or any other human influenza viruses. We investigated the frequency of oseltamivir and zanamivir resistance in circulating seasonal influenza A (H1N1) viruses in Australasia and Southeast Asia. Analysis of 391 influenza A (H1N1) viruses isolated between 2006 and early 2008 from Australasia and Southeast Asia revealed nine viruses (2.3%) that demonstrated markedly reduced zanamivir susceptibility and contained a previously undescribed Gln136Lys (Q136K) neuraminidase mutation. The mutation had no effect on oseltamivir susceptibility but caused approximately a 300-fold and a 70-fold reduction in zanamivir and peramivir susceptibility, respectively. The role of the Q136K mutation in conferring zanamivir resistance was confirmed using reverse genetics. Interestingly, the mutation was not detected in the primary clinical specimens from which these mutant isolates were grown, suggesting that the resistant viruses either occurred in very low proportions in the primary clinical specimens or arose during MDCK cell culture passage. Compared to susceptible influenza A (H1N1) viruses, the Q136K mutant strains displayed greater viral fitness than the wild-type virus in MDCK cells but equivalent infectivity and transmissibility in a ferret model.