Induction therapy in renal transplant recipients: a review.

Transplant science has improved significantly over the last decade. Influenced by novel advancements, rejection rates and short-term graft losses diminished substantially. Induction therapy was shown to reduce rejection rates and improve short-term graft survival. In this article, we discuss the most commonly used induction agents and the choice of induction therapy in different renal transplant recipient subgroups. The medical literature as well as our own experience was used to prepare this review. At this time, induction therapy is commonly used in upwards of 80%, of renal transplant recipients. Depleting agents are the most frequently used agents and they account for more than 75% of all induction therapies in the United States. Currently, there is no consensus regarding the choice of induction therapy. The type of induction therapy is generally selected based on a comprehensive evaluation of the recipient and the donor's immunological risks, the risk of developing opportunistic infection and malignancy, recipient comorbidities, financial burden and the choice of maintenance immunosuppressive regimen.

Blocking S-adenosylmethionine synthesis in yeast allows selenomethionine incorporation and multiwavelength anomalous dispersion phasing.

Saccharomyces cerevisiae is an ideal host from which to obtain high levels of posttranslationally modified eukaryotic proteins for x-ray crystallography. However, extensive replacement of methionine by selenomethionine for anomalous dispersion phasing has proven intractable in yeast. We report a general method to incorporate selenomethionine into proteins expressed in yeast based on manipulation of the appropriate metabolic pathways. sam1(-) sam2(-) mutants, in which the conversion of methionine to S-adenosylmethionine is blocked, exhibit reduced selenomethionine toxicity compared with wild-type yeast, increased production of protein during growth in selenomethionine, and efficient replacement of methionine by selenomethionine, based on quantitative mass spectrometry and x-ray crystallography. The structure of yeast tryptophanyl-tRNA synthetase was solved to 1.8 A by using multiwavelength anomalous dispersion phasing with protein that was expressed and purified from the sam1(-) sam2(-) strain grown in selenomethionine. Six of eight selenium residues were located in the structure.

Analysis of the 2.0 A crystal structure of the protein-DNA complex of the human PDEF Ets domain bound to the prostate specific antigen regulatory site.

PDEF, a prostate epithelial specific transcription factor, is a member of the Ets family of DNA binding proteins. Here we report a 2.0 A crystal structure of the PDEF Ets domain in complex with a natural, high-affinity DNA binding site in the promoter/enhancer region of the human prostate specific antigen gene. Comparison of the PDEF-DNA complex with other Ets complexes revealed key features that are shared among Ets members, as well as important differences in substrate specification at both the "GGA" core and the flanking regions of the DNA site. The combination of the serine residue at position 308 and the glutamine at position 311 explains the previous observation that the PDEF binds preferentially to a thymine at the +4 position of its binding site. Despite the common essential features that are shared among Ets members, PDEF demonstrates distinct patterns of interactions at different positions of DNA in achieving sequence specific recognition. Collectively, the common and unique interactions with both the DNA bases and the backbone phosphates lead to substrate specificity and individual preference for certain DNA sites.