Development of alternative reality environments for spacecraft habitat design evaluation

Virtual Reality - Alternative reality (XR) tools are becoming more commonplace in the realm of architecture, engineering, and construction (AEC); however, these digitally immersive technologies...     

CoMFA methodology in structure-activity analysis of hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives based on affinity towards 5-HT1A, 5-HT2A and alpha1-adrenergic receptors

Structural features of the pyrido[1,2-c]pyrimidine derivatives with arylpiperazine moiety and their affinities towards 5-HT1A, 5-HT2A and alpha1-adrenergic receptors were analyzed using the CoMFA procedure. On the basis of 3D-QSAR models for the 5-HT2A and alpha1-adrenergic receptors, four compounds with expected better affinity/selectivity were proposed and synthesized. The affinities obtained confirm experimentally the usefulness of CoMFA models. Our results suggest that active conformations adopted by the studied molecules when interacting with the receptors are neutral instead of the protonated ones.     

Evidence that a novel thioesterase is responsible for polyketide chain release during biosynthesis of the polyether ionophore monensin

Polyether ionophores, such as monensin A, are known to be biosynthesised, like many other antibiotic polyketides, on giant modular polyketide synthases (PKSs), but the intermediates and enzymes involved in the subsequent steps of oxidative cyclisation remain undefined. In particular there has been no agreement on the mechanism and timing of the final polyketide chain release. We now report evidence that MonCII from the monensin biosynthetic gene cluster in Streptomyces cinnamonensis, which was previously thought to be an epoxide hydrolase, is a novel thioesterase that belongs to the alpha/beta-hydrolase structural family and might catalyse this step. Purified recombinant MonCII was found to hydrolyse several thioester substrates, including an N-acetylcysteamine thioester derivative of monensin A. Further, incubation with a hallmark inhibitor of such enzymes, phenylmethanesulfonyl fluoride, led to inhibition of the thioesterase activity and to the accumulation of an acylated form of MonCII. These findings require a reassessment of the role of other enzymes implicated in the late stages of polyether ionophore biosynthesis.