Background: KATmt is the first identified cAMP-regulated protein lysine acetylase in mycobacteria. Results: KATmt acylates fatty acyl CoA ligases in vivo in a cAMP-dependent manner, thus regulating their activity. Conclusion: Mycobacteria utilize KATmt to regulate the metabolic pool of acetyl and propionyl CoA. Significance: We provide novel paradigms for linking cAMP signaling and fatty acid metabolism in mycobacteria.

The kinesin-3 KIF1C is a fast organelle transporter implicated in the transport of dense core vesicles in neurons and the delivery of integrins to cell adhesions. Here we report the mechanisms of autoinhibition and release that control the activity of KIF1C. We show that the microtubule binding surface of KIF1C motor domain interacts with its stalk and that these autoinhibitory interactions are released upon binding of protein tyrosine phosphatase PTPN21. The FERM domain of PTPN21 stimulates dense core vesicle transport in primary hippocampal neurons and rescues integrin trafficking in KIF1C-depleted cells. In vitro, human full-length KIF1C is a processive, plus-end directed motor. Its landing rate onto microtubules increases in the presence of either PTPN21 FERM domain or the cargo adapter Hook3 that binds the same region of KIF1C tail. This autoinhibition release mechanism allows cargo-activated transport and might enable motors to participate in bidirectional cargo transport without undertaking a tug-of-war.

Abstract-Intracellular transport along microtubules enables cellular cargoes to efficiently reach the extremities of large, eukaryotic cells. While it would take more than 200 years for a small vesicle to diffuse from the cell body to the growing tip of a one meter long axon, transport by a kinesin allows delivery in one week. It is clear from this example that the evolution of intracellular transport was tightly linked to the development of complex and macroscopic life forms. The human genome encodes 45 kinesins, 8 of those belonging to the family of kinesin 3 organelle transporters that are known to transport a vari ety of cargoes towards the plus end of microtubules. However, their mode of action, their tertiary structure, and regulation are controversial. In this review, we summarize the latest developments in our understanding of these fascinating molecular motors.

Background: Cyclic AMP allosterically modulates GNAT-like acyltransferases (KAT) in mycobacteria. Results: Structures of the protein from M. smegmatis and its mutants are described. Conclusion: The divergent properties of KATs from M. tuberculosis and M. smegmatis are the result of differential conformational dynamics in the two proteins. Significance: Apparently similar proteins show subtle differences in their structural features, having evolved based on the needs of the organism.

Dietary isoflavones, popularly known as phytoestrogens, represent one of the most biologically active classes of flavonoids. Numerous in vitro and in vivo studies provide convincing evidence regarding their beneficial effects on human health. These isoflavones are increasingly being investigated as potential alternate therapies for a range of hormone-dependent conditions, including cancer, menopausal symptoms, osteoporosis and cardiovascular diseases. However, they exhibit poor oral bioavailability which limits their clinical utility in humans. The reason being, they are substrates of a plethora of enzymes and transporters and undergo extensive conjugative metabolism which facilitates their rapid elimination from biological systems. In addition, a number of experimental studies have also revealed that these isoflavones are potent inhibitors of various cytochrome P450 isoforms and transporters which play an important role in the disposition of many commonly prescribed drugs. Thus, there arise chances of observing clinically relevant herb-drug interactions which could sometimes be life-threatening. This review gives a comprehensive understanding of these dietary phytoestrogens with regard to their absorption, biodistribution and the role of enzyme-transporter interplay affecting their disposition in biological systems. Further, the effects of these phytoestrogens on the activity and kinetics of drug metabolizing enzymes and various clinically relevant influx/efflux transporters and the resulting diet-drug interactions have also been discussed.