Published in Bioorganic & medicinal chemistry letters
Discovery of novel classes of Gram-negative antibiotics with activity against multi-drug resistant infections is a critical unmet need. As an essential member of the lipoprotein biosynthetic pathway, lipoprotein signal peptidase II (LspA) is an attractive target for antibacterial drug discovery, with the natural product inhibitor globomycin offerin...
Published in Methods in molecular biology (Clifton, N.J.)
Chemogenomic profiling is a powerful and unbiased approach to elucidate pharmacological targets and the mechanism of bioactive compounds. It is based on identifying cellular hypersensitivity and resistance caused by individual gene modulations with genome-wide coverage. Due to the requirement of bar-coded, genome-wide deletion collections, high-res...
Published in Methods in enzymology
Signal peptidases are membrane proteases that play crucial roles in the protein transport pathway of bacteria. They cleave off the signal peptide from precursor proteins that are membrane inserted by the SecYEG or Tat translocons. Signal peptide cleavage releases the translocated protein from the inner membrane allowing the protein to be exported t...
Published in BMC medical imaging
L. monocytogenes encodes three orthologous signal peptidases of Type I (SPases I). SipZ improves the secretion efficiency for a subset of extracellular virulence factors. Multiple SPases I are functionally redundant for the majority of the Sec-secreted exoproteins of L. monocytogenes. The concepts of major and minor SPases are not absolute but rela...
Published in Bioorganic & medicinal chemistry letters
New antibiotics are needed, and one source may be 'latent' antibiotics, natural products whose once broad-spectrum activity is currently limited by the evolution of resistance in nature. We have identified a potential class of latent antibiotics, the arylomycins, which are lipopeptides with a C-terminal macrocycle that target signal peptidase and w...
Published in Biochemical and Biophysical Research Communications
Tuberculosis (TB) is the second highest cause of mortality after HIV/AIDS and is one of the leading public health problems worldwide. The growing resistance to anti-TB drugs and the recalcitrant nature of tenacious infections present arduous challenges for the treatment of TB. Thus, the need to develop therapeutics against novel drug targets to hel...
Published in Analytical Biochemistry
All species of the genus Rhodnius have a characteristic red coloration in their salivary glands due to the presence of heme proteins. Some of these secreted proteins, known as nitrophorins (NPs), are responsible for many of the antihemostatic activities of Rhodnius saliva such as anticoagulant and antihistamine. Several NPs have been described (NP1...
Type I signaalpeptidases (SPasesI) spelen een essentiële rol in eiwitsec retie aangezien deze enzymen verantwoordelijk zijn voor de afsplitsing v an de N-terminale signaalpeptiden van secretorische eiwitten na hun tran sport over een biologische membraan. Bacteriële SPasesI worden beschouwd als een interessant antibacterieel doelwit omwille van hun...
Published in FEMS microbiology letters
Yersinia pestis PsaA is an adhesin important for the establishment of bacterial infection. PsaA synthesis requires the products of the psaEFABC genes. Here, by prediction analysis, we identified a PsaA signal sequence with two signal peptidase (SPase) cleavage sites, type-I and type-II (SPase-I and SPase-II). By Edman degradation and site-directed ...
Published in BBA - Biomembranes
Many of the recent advancements in the field of protein translocation, particularly from the structural perspective, have relied on Archaea. For instance, the solved structures of the translocon from the methanoarchaeon Methanocaldococcus jannaschii of the ribosomal large subunit from the haloarchaeon Haloarcula marismortui and of components of the...
