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Highlights: [•] N-(2-mercaptopropionyl)-glycine (NMPG), a diffusible anti-oxidant, ameliorates TNBS-induced rat colitis. [•] NMPG activates an ulcer healing pathway, HIF-1-VEGF. [•] NMPG stabilizes HIF-1α protein by inhibiting HIF prolyl hydroxylase-2 (HPH-2). [•] NMPG inhibition of HPH-2 is attenuated by ascorbate, a cofactor of the enzyme. [ABSTRACT FROM AUTHOR]

Abstract: Wnt/β-catenin signaling controls a variety of cellular processes, including cell growth, oncogenesis, and development. Upon Wnt stimulation, the intracellular region of the coreceptor, LRP6 or 5, is phosphorylated by the membrane-recruited GSK3β and CK1. The cytoplasmic domain of LRP6/5 contains one Ser/Thr cluster and the PPPSP motifs, both of which are essential for propagation of the signal. While the phosphorylated PPPSP motifs are known to directly inhibit GSK3β, the biochemical role of the phosphorylated Ser/Thr cluster remains to be elucidated. Herein, we reveal that the Ser/Thr cluster plays an important role in the phosphorylation of the PPPSP motif. Interestingly, we observe that GSK3β activity on the PPPSP motif requires a high ATP concentration, close to that of the physiological condition. Taken together, these data suggest that the phosphorylated Ser/Thr cluster serves as a docking site for GSK3β to promote the phosphorylation of the PPPSP motif. Our results provide insight into the molecular mechanism for the initial events of the Wnt/β-catenin signaling. [Copyright &y& Elsevier]

Abstract: Lysozymes are an important component of the innate immune system of animals that hydrolyze peptidoglycan, the major bacterial cell wall constituent. Many bacteria have contrived various means of dealing with this bactericidal enzyme, one of which is to produce lysozyme inhibitors. Recently, a novel family of bacterial lysozyme inhibitors was identified in various Gram-negative bacteria, named MliC (membrane bound lysozyme inhibitor of C-type lysozyme). Here, we report the crystal structure of Pseudomonas aeruginosa MliC in complex with chicken egg white lysozyme. Combined with mutational study, the complex structure demonstrates that the invariant loop of MliC plays a crucial role in the inhibition of the lysozyme by its insertion to the active site cleft of the lysozyme, where the loop forms hydrogen and ionic bonds with the catalytic residues. Since MliC family members have been implicated as putative colonization or virulence factors, the structures and mechanism of action of MliC will be of relevance to the control of bacterial growth in animal hosts. [Copyright &y& Elsevier]