Biochemistry

Molecular determinants of Neu5Ac binding to a tripartite ATP independent periplasmic (TRAP) transporter

1. Parveen Goyal
2. KanagaVijayan Dhanabalan
3. Mariafrancesca Scalise
4. Rosmarie Friemann
5. Cesare Indiveri
6. Renwick CJ Dobson
7. Kutti R Vinothkumar
8. Subramanian Ramaswamy

• Curated by eLife

  eLife Assessment

  This valuable work provides novel insights into the substrate binding mechanism of a tripartite ATP-independent periplasmic (TRAP) transporter, which may be helpful for the development of specific inhibitors. The structural analysis is convincing, but additional work will be required to establish the transport mechanism as well as well as binding sites for all ligands. This study will be of interest to the membrane transport and bacterial biochemistry communities.

Reviewed by eLife

Reduction of DNA Topoisomerase Top2 Reprograms the Epigenetic Landscape and Extends Health and Life Span Across Species

1. Man Zhu
2. Meng Ma
3. Lunan Luo
4. Feiyang Li
5. Jiashun Zheng
6. Yan Pan
7. Lu Yang
8. Ying Xiao
9. Ziyan Wang
10. Bo Xian
11. Yi Zheng
12. Hao Li
13. Jing Yang

• Curated by eLife

  eLife Assessment

  Building on earlier evidence that Topoisomerase 2 depletion can extend yeast lifespan, the authors present convincing data demonstrating that reduced Top2 levels confer significant longevity benefits in C. elegans and mice. They show that these benefits encompass not only extended survival but also improved healthspan and mitigation of aging phenotypes, supported by robust transcriptomic, epigenetic, and histological analyses. While the exact mechanistic underpinnings-such as the potential connection to classical aging pathways and the selective down-regulation of genes with active promoters-remain to be fully elucidated, the breadth of these important findings strongly indicates a conserved role for Top2 in aging regulation.

Reviewed by eLife

Alzheimer-mutant γ-secretase complexes stall amyloid β-peptide production

1. Parnian Arafi
2. Sujan Devkota
3. Emily Williams
4. Masato Maesako
5. Michael S Wolfe

• Curated by eLife

  eLife Assessment

  This manuscript provides fundamental studies to gain insight into the mutations in the presenilin-1 (PSEN1) gene on proteolytic processing of the amyloid precursor protein (APP). The authors provide compelling evidence using mutations in PSEN to understand what drives alternative substrate turnover with convincing data and rigorous analysis. This deep mechanistic study provides a framework towards the development of small molecule inhibitors to treat AD.

Reviewed by eLife

Enzymatic access to the rare ΔUA (1→4) Glc 3, 6, N-sulfated heparin disaccharide, implications for heparin quality control

1. T. K. Kandola
2. C. J. Mycroft-West
3. M. L. Andrade De Lima
4. A. Turner
5. C. Gardini
6. E. Urso
7. G.J. Miller
8. A. Bisio
9. E. A. Yates
10. M. Guerrini
11. L. Wu
12. M. A. Skidmore

Reviewed by preLights

Curcuma longa Essential Oil Topically Mitigates Inflammatory Markers in Acetone-Induced Atopic Dermatitis in Wistar Albino Rats

1. Nathiim Namale
2. Deusdedit Tusubira
3. Kenneth Male
4. Angela Mumbua Musyoka
5. Patrick Maduabuchi Aja

Reviewed by Arcadia Science

Paradoxical dominant negative activity of an immunodeficiency-associated activating PIK3R1 variant

1. Patsy R Tomlinson
2. Rachel G Knox
3. Olga Perisic
4. Helen Su
5. Gemma V Brierley
6. Roger L Williams
7. Robert K Semple

• Curated by eLife

  eLife Assessment

  This important study reports on PI3KR mutations and a paradoxical mechanism of PI3KR signaling. The strength of evidence for the study is mostly convincing, as conclusions are supported by a variety of mutational strategies and cellular systems to look at interactions among signaling pathways.

Reviewed by eLife

The conserved biochemical activity and function of an early metazoan phosphatidylinositol 5 phosphate 4-kinase regulates growth and development

1. Harini Krishnan
2. Suhail Muzaffar
3. Sanjeev Sharma
4. Visvanathan Ramya
5. Avishek Ghosh
6. Ramanathan Sowdhamini
7. Padinjat Raghu

Reviewed by Review Commons

Medium-sized protein language models perform well at transfer learning on realistic datasets

1. Luiz C. Vieira
2. Morgan L. Handojo
3. Claus O. Wilke

Reviewed by Arcadia Science

Acetylation-Primed SUMOylation Drives RORβ Turnover via a p300-SIRT1 Regulatory Axis

1. Timothy R. O’Leary
2. Denis Shutin
3. Nadeska I. Montalvan
4. Nereida M. Abad-Yang
5. Vuong Dang
6. Dean P. Edwards
7. Patrick R. Griffin
8. Mi Ra Chang

Reviewed by Arcadia Science

Computational enzyme design by catalytic motif scaffolding

1. Markus Braun
2. Adrian Tripp
3. Morakot Chakatok
4. Sigrid Kaltenbrunner
5. Celina Fischer
6. David Stoll
7. Aleksandar Bijelic
8. Wael Elaily
9. Massimo G. Totaro
10. Melanie Moser
11. Shlomo Y. Hoch
12. Horst Lechner
13. Federico Rossi
14. Matteo Aleotti
15. Mélanie Hall
16. Gustav Oberdorfer

Reviewed by PREreview