The mitochondrial permeability transition pore (PT pore) is a recognised drug target for neurodegenerative conditions such as multiple sclerosis (MS) and for ischaemia–reperfusion injury in the brain and heart. The peptidylprolyl isomerase, cyclophilin D (CypD, ppif) is a positive regulator of the pore and genetic downregulation or knockout improves outcomes in disease models. Current inhibitor...

Peptidoglycan hydrolases are key enzymes in bacterial cell wall homeostasis. Understanding the substrate specificity and biochemical activity of peptidoglycan hydrolases in Mycobacterium tuberculosis is of special interest as it can aid in the development of new cell wall targeting therapeutics. In this study, we report biochemical and structural characterization of the mycobacterial Nacetylmur...

Heme-derived linear tetrapyrroles (phytobilins) in phycobiliproteins and phytochromes perform critical light-harvesting and light-sensing roles in oxygenic photosynthetic organisms. A key enzyme in their biogenesis, phycocyanobilin:ferredoxin oxidoreductase (PcyA), catalyzes the overall four-electron reduction of biliverdin IXR to phycocyanobilin;the common chromophore precursor for both classe...

Waterfowl, including ducks, geese, rails and others, are host to a great diversity of ectosymbiotic arthropods. In this study, we collected ectosymbionts from waterfowl and analyzed taxon richness and total abundance to determine whether there were differences in the mite and louse assemblages of waterfowl of different species, genera, sexes, and feeding behaviors. Data were collected from 53 i...

Small G-proteins (G) of the Ras-superfamily control the temporal and spatial coordination of intracellular signaling networks by acting as molecular on/off switches. Guanine nucleotide exchange factors (GEFs) regulate the activation of these G-proteins through catalytic replacement of guanosine diphosphate (GDP) by guanosine triphosphate (GTP). During nucleotide exchange, three distinct substra...

Vaccinia virus (VACV) encodes several proteins that inhibit activation of the proinflammatory transcription factor nuclear factor κB (NF-κB). VACV protein A49 prevents translocation of NF-κB to the nucleus by sequestering cellular β-TrCP, a protein required for the degradation of the inhibitor of κB. A49 does not share overall sequence similarity with any protein of known structure or function....

Elevated levels of the tumor marker S100B are observed in malignant melanoma, and this EF-hand-containing protein was shown to directly bind wild-type (wt) p53 in a Ca-dependent manner, dissociate the p53 tetramer, and inhibit its tumor suppression functions. Likewise, inhibiting S100B with small interfering RNA (siRNA) is sufficient to restore wild-type p53 levels and its downstream gene produ...

Peptidoglycan (PG) modifying carboxypeptidases (CPs) are important determinants of bacterial cell shape. Here, we report crystal structures of Csd4, a threedomain protein from the human gastric pathogen Helicobacter pylori. The catalytic zinc in Csd4 is coordinated by a rare H+E+Q configuration that is conserved amongst most Csd4 homologs, which form a distinct subfamily of CPs. Substitution of...

To get insight on archaeal nitrogen signaling and on haloadaptation of the nitrogen/carbon/energy-signaling protein PII, we determined crystal structures of recombinantly produced GlnK2 from the extreme halophilic archaea Haloferax mediterranei, complexed with AMP or with the PII effectors ADP or ATP, at respective resolutions of 1.49, 1.45 and 2.60 Å. A unique A cc ep te d A rt ic le This arti...

Adherence of bacteria to biotic or abiotic surfaces is a prerequisite for host colonization and represents an important step in microbial pathogenicity. This attachment is facilitated by bacterial adhesins at the cell surface. Due to their size and often elaborate multi-domain architectures, these polypeptides represent challenging targets for detailed structural and functional characterization...