Bacteria thrive in diverse environments and must withstand various stresses. A key stress response mechanism is the reprogramming of macromolecular biosynthesis and metabolic processes through alarmones - signaling nucleotides that accumulate intracellularly in response to metabolic stress. Diadenosine tetraphosphate (Ap4A), a putative alarmone, is produced in a noncanonical reaction by universally conserved aminoacyl-tRNA synthetases. Ap4A is ubiquitous across all domains of life and accumulates during heat and oxidative stress. Despite its early discovery in 1966, Ap4A's alarmone status remained inconclusive. Recent discoveries identified Ap4A as a precursor to RNA 5' caps in Escherichia coli. Additionally, Ap4A was found to directly bind to and allosterically inhibit the purine biosynthesis enzyme inosine 5'-monophosphate dehydrogenase, regulating guanosine triphosphate levels and enabling heat resistance in Bacillus subtilis. These findings, along with previous research, strongly suggest that Ap4A plays a crucial role as an alarmone, warranting further investigation to fully elucidate its functions.

2023-08-01·Biochemistry

Insights into Enzymatic Catalysis from Binding and Hydrolysis of Diadenosine Tetraphosphate by E. coli Adenylate Kinase.

Article

作者: Tischlik, Sonja ; Oelker, Melanie ; Sauer-Eriksson, A Elisabeth ; Drescher, Malte ; Rogne, Per ; Wolf-Watz, Magnus

Adenylate kinases play a crucial role in cellular energy homeostasis through the interconversion of ATP, AMP, and ADP in all living organisms. Here, we explore how adenylate kinase (AdK) from Escherichia coli interacts with diadenosine tetraphosphate (AP4A), a putative alarmone associated with transcriptional regulation, stress, and DNA damage response. From a combination of EPR and NMR spectroscopy together with X-ray crystallography, we found that AdK interacts with AP4A with two distinct modes that occur on disparate time scales. First, AdK dynamically interconverts between open and closed states with equal weights in the presence of AP4A. On a much slower time scale, AdK hydrolyses AP4A, and we suggest that the dynamically accessed substrate-bound open AdK conformation enables this hydrolytic activity. The partitioning of the enzyme into open and closed states is discussed in relation to a recently proposed linkage between active site dynamics and collective conformational dynamics.

2021-10-01·Eating and weight disorders : EWD3区 · 医学

Parental perceptions of actual and ideal body weight in early childhood prospectively predict adolescent perceptions of actual and ideal body weight among a low-income population

3区 · 医学

Article

作者: Barry, Mikayla R ; Miller, Alison L ; Hahn, Samantha L ; Weeks, Heidi M ; Lumeng, Julie C ; Sonneville, Kendrin R

PURPOSE:

To examine the longitudinal associations between parental perceptions of their child's actual weight (PPCA = parental perception of child's actual) and ideal weight (PPCI = parental perception of child ideal) in early childhood and the child's own perceptions of their actual weight (APA = adolescent perceived actual) and ideal weight (API = adolescent perceived ideal) during early adolescence among a low-income population.

METHODS:

Using a longitudinal study design, 136 child/parent pairs were asked to assess the child's actual and ideal weight using figure rating scales. When children were 4-7 years old, parents reported on their perception of their child's weight; when children were 10-12 years old, the child reported on their own weight perceptions. Actual weight, ideal weight, and the difference between ideal and actual weight perception were assessed at the respective timepoints. Regressions were used to examine the relationship between parental weight perceptions (PPCA and PPCI) and later adolescent weight perception (APA and API).

RESULTS:

On average, PPCI was higher than PPCA, whereas API was lower than APA. We found a positive relationship between PPCI and API (β = 0.309, p = .029). PPCA was positively associated with API (β = 0.304, p = .015) and marginally positively associated with the APA (β = 0.242, p = .077). However, the difference between PPCI and PPCA did not predict either APA or API.

CONCLUSIONS:

Parental perception of their child's weight may relate to the adolescent's weight perception, particularly ideal weight. However, several null and marginal associations suggest that parental weight perception in early childhood may not be the most salient factor in determining weight perception in early adolescence.

LEVEL OF EVIDENCE:

Level III, well-designed longitudinal cohort study.

100 项与 99mTc-APA 相关的药物交易

登录后查看更多信息