Allomorphy as a mechanism of post-translational control of enzyme activity

Enzyme regulation is vital for metabolic adaptability in living systems. Fine control of enzyme activity is often delivered through post-translational mechanisms, such as allostery or allokairy. β-phosphoglucomutase (βPGM) from Lactococcus lactis is a phosphoryl transfer enzyme required for complete catabolism of trehalose and maltose, through the isomerisation of β-glucose 1-phosphate to glucose 6-phosphate via β-glucose 1,6-bisphosphate. Surprisingly for a gatekeeper of glycolysis, no fine control mechanism of βPGM has yet been reported. Herein, we describe allomorphy, a post-translational control mechanism of enzyme activity. In βPGM, isomerisation of the K145-P146 peptide bond results in the population of two conformers that have different activities owing to repositioning of the K145 sidechain. In vivo phosphorylating agents, such as fructose 1,6-bisphosphate, generate phosphorylated forms of both conformers, leading to a lag phase in activity until the more active phosphorylated conformer dominates. In contrast, the reaction intermediate β-glucose 1,6-bisphosphate, whose concentration depends on the β-glucose 1-phosphate concentration, couples the conformational switch and the phosphorylation step, resulting in the rapid generation of the more active phosphorylated conformer. In enabling different behaviours for different allomorphic activators, allomorphy allows an organism to maximise its responsiveness to environmental changes while minimising the diversion of valuable metabolites

HPV testing: a mixed-method approach to understand why women prefer self-collection in a middle-income country

Abstract Background HPV test self-collection has been shown to reduce barriers to cervical screening and increase uptake. However, little is known about women’s preferences when given the choice between self-collected and clinician-collected tests. This paper aims to describe experiences with HPV self-collection among women in Jujuy, the first Argentinean province to have introduced HPV testing as the primary screening method, provided free of cost in all public health centers. Methods Between July and December 2012, data on acceptability of HPV self-collection and several social variables including past screening were collected from 2616 self-collection accepters and 433 non-accepters, and were analyzed using multivariate regression. In addition, in-depth interviews (n = 30) and 2 focus groups were carried out and analyzed using thematic analysis. Results Quantitative findings indicate that main reasons for choosing self-collection are those reducing barriers related to women’s roles of responsibility for domestic work and work/family organization, and to health care services’ organization. No social variables were significantly associated with acceptability. Among those who preferred clinician-collection, the main reasons were trust in health professionals and fear of hurting themselves. Qualitative findings also showed that self-collection allows women to overcome barriers related to the health system (i.e. long wait times), without sacrificing time devoted to work/domestic responsibilities. Conclusions Findings have implications for self-collection recommendations, as they show it is the preferred method when women are given the choice, even if they are not screening non-attenders. Findings also highlight the importance of incorporating women’s needs/preferences in HPV screening recommendations