Docking domains (DDs) located at the C- and N-termini of polypeptides play a crucial role in directing the assembly of polyketide synthases (PKSs), which are multienzyme complexes. Here, we determined the crystal structure of a complex comprising the C-terminal DD (DD) and N-terminal DD (DD) of macrolactin trans-acyltransferase (AT) PKS that were fused to a functional enzyme, AmpC EC2 β-lactamase. Interface analyses of the DD/DD complex revealed the molecular intricacies in the core section underpinning the precise DD assembly.
View Article and Find Full Text PDFObjectives: Stenotrophomonas spp. intrinsically resistant to many β-lactam antibiotics are found throughout the environment. CESS-1 identified in Stenotrophomonas sp.
View Article and Find Full Text PDFPhosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P] is implicated in various processes, including hormone-induced signal transduction, endocytosis, and exocytosis in the plasma membrane. However, how HO accumulation regulates the levels of PtdIns(4,5)P in the plasma membrane in cells stimulated with epidermal growth factors (EGFs) is not known. We show that a plasma membrane PtdIns(4,5)P-degrading enzyme, synaptojanin (Synj) phosphatase, is inactivated through oxidation by HO.
View Article and Find Full Text PDFFibroblast growth factor 21 (FGF21) has pharmaceutical potential against obesity-related metabolic disorders, including non-alcoholic fatty liver disease. Since thermal stability is a desirable factor for therapeutic proteins, we investigated the thermal behavior of human FGF21. FGF21 remained soluble after heating; thus, we examined its temperature-induced structural changes using circular dichroism (CD).
View Article and Find Full Text PDFArch Biochem Biophys
October 2020
The hydrolysis of β-lactam antibiotics by class C β-lactamases proceeds through the acylation and the rate-determining deacylation steps mediated by the nucleophilic serine and the deacylation water, respectively. The pose of poor substrates such as carbapenems in the acylated enzyme is responsible for the low efficient deacylation reaction. Here we present the crystal structures of the Y150F variant of the ACC-1 class C β-lactamase in the apo and acylated states.
View Article and Find Full Text PDFFront Cell Infect Microbiol
September 2019
β-Lactamase-mediated resistance to β-lactam antibiotics has been significantly threatening the efficacy of these clinically important antibacterial drugs. Although some β-lactamase inhibitors are prescribed in combination with β-lactam antibiotics to overcome this resistance, the emergence of enzymes resistant to current inhibitors necessitates the development of novel β-lactamase inhibitors. In this study, we evaluated the inhibitory effect of dinucleotides on an extended-spectrum class C β-lactamase, AmpC BER.
View Article and Find Full Text PDF