Combination of solution and solid state NMR yields a molecular level view of the interactions between antibiotic teixobactin and bacterial cell wall building block lipid II.

Penicillin binding proteins (PBPs) catalysing transpeptidation reactions that stabilize the peptidoglycan component of the bacterial cell wall are the targets of -lactams, the most clinically successful antibiotics to date. However, PBP-transpeptidation enzymology has evaded detailed analysis, because of the historical unavailability of kinetically competent assays with physiologically relevant substrates and the previously unappreciated contribution of protein cofactors to PBP activity. By re-engineering peptidoglycan synthesis, we have constructed a continuous spectrophotometric assay for transpeptidation of native or near native peptidoglycan precursors and fragments by Escherichia coli PBP1B, allowing us to (a) identify recognition elements of transpeptidase substrates, (b), reveal a novel mechanism of stereochemical editing within peptidoglycan transpeptidation, (c) assess the impact of peptidoglycan substrates on -lactam targeting of transpeptidation and (d) demonstrate both substrates have to be bound before transpeptidation occurs. The results allow characterization of high molecular weight PBPs as enzymes and not merely the targets of -lactam acylation.

Human chorionic gonadotropin beta subunit (CGB) is a marker of pregnancy as well as trophoblastic and nontrophoblastic tumors. CGB is encoded by a cluster of six genes, of which type II genes (CGB3/9, 5 and 8) have been shown to be upregulated in relation to type I genes (CGB6/7) in both placentas and tumors. Recent studies revealed that CGB1 and CGB2, originally considered as pseudogenes, might also be active, however, the protein products of these genes have not yet been identified. Our study demonstrates the presence of CGB1 and CGB2 transcripts in ovarian carcinomas. While CGB1 and CGB2 gene activation was not detected in normal ovaries lacking cancerous development, our study demonstrates the presence of CGB1 and CGB2 transcripts in 41% of analyzed ovarian cancer cases.

No abstract