Crystal structures of the protease of human immunodeficiency virus type 1 (HIV-1) and two mutant proteases, V82D and V82N, have been determined. In all three cases the enzyme forms a complex with the peptidic inhibitor U-89360E. All structures have been determined to 2.3 Å resolution and have satisfactory agreement factors: 0.173 for wild type, 0.175 for V82D, and 0.182 for V82N. Comparison of the three crystal structures provides explanations which are consistent with the known kinetic properties of these mutant enzymes with the U-89360E inhibitor [

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Aim To understand the underlying pathology and antenatal, intrapartum and postnatal issues associated with Fanconi anaemia, and to appreciate the importance of care planning and MDT working. Discussion Described first in 1927, Fanconi anaemia is one of an autosomal recessive group of inherited bone marrow failure syndromes. It is characterised by dysmorphic features, pancytopenic bone marrow failure, and susceptibility to certain malignancies. It can be associated with delayed puberty, primary infertility and premature menopause, with limited data on pregnancy management. We present a case of a 23 year old primigravida with pre-existing Fanconi Anaemia. She was known to have severe thrombocytopenia and anaemia, both transfusion dependent. Despite relative stability pre-pregnancy her obstetric course was complicated by superimposed pre-eclampsia and worsening pancytopenia. Issues were further complicated by ceasing her pre-pregnancy androgens which had maintained her platelet count. Antenatal care was managed in a specialist joint haematology clinic with support from national centres and the local blood transfusion service. Additionally potential fetal implications of Fanconi anaemia were considered with the neonatology team. Considerable thought and planning was given to her mode of delivery and intrapartum blood product requirements. The risks and benefits of operative vs. vaginal delivery were debated, with elective Caesarean Section chosen. Post pregnancy follow up included detailed discussion of future contraception leading to hysteroscopic sterilisation. Conclusion Fanconi anaemia presents many fetal and maternal challenges to the management of pregnancy. Managing rare complex cases such as this not only requires detailed planning but also excellent inter-disciplinary team communication.

Mammalian Elongin B is a 118-amino acid protein composed of an 84-amino acid amino-terminal ubiquitin-like domain and a 34-amino acid carboxyl-terminal tail. Elongin B is found in cells as a subunit of the heterodimeric Elongin BC complex, which was originally identified as a positive regulator of RNA polymerase II elongation factor Elongin A and subsequently as a component of the multiprotein von Hippel-Lindau tumor suppressor and suppressor of cytokine signaling complexes. As part of our effort to understand how the Elongin BC complex regulates the activity of Elongin A, we are characterizing Elongin B functional domains. In this report, we show that the Elongin B ubiquitin-like domain is necessary and sufficient for interaction with Elongin C and for positive regulation of Elongin A transcriptional activity. In addition, by site-directed mutagenesis of the Elongin B ubiquitin-like domain, we identify a short Elongin B region that is important for its interaction with Elongin C. Finally, we observe that both the ubiquitin-like domain and carboxyl-terminal tail are conserved in Drosophila melanogaster and Caenorhabditis elegans Elongin B homologs that efficiently substitute for mammalian Elongin B in reconstitution of the transcriptionally active Elongin ABC complex, suggesting that the carboxyl-terminal tail performs an additional function not detected in our assays.