Biochemistry

The mechanism of RNA capping by SARS-CoV-2

1. Gina J. Park
2. Adam Osinski
3. Genaro Hernandez
4. Jennifer L. Eitson
5. Abir Majumdar
6. Marco Tonelli
7. Katie Henzler-Wildman
8. Krzysztof Pawłowski
9. Zhe Chen
10. Yang Li
11. John W. Schoggins
12. Vincent S. Tagliabracci

Reviewed by ScreenIT

The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and x-ray diffraction at room temperature

1. Galen J. Correy
2. Daniel W. Kneller
3. Gwyndalyn Phillips
4. Swati Pant
5. Silvia Russi
6. Aina E. Cohen
7. George Meigs
8. James M. Holton
9. Stefan Gahbauer
10. Michael C. Thompson
11. Alan Ashworth
12. Leighton Coates
13. Andrey Kovalevsky
14. Flora Meilleur
15. James S. Fraser

Reviewed by ScreenIT

Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19

1. Jonathan H. Shrimp
2. John Janiszewski
3. Catherine Z. Chen
4. Miao Xu
5. Kelli M. Wilson
6. Stephen C. Kales
7. Philip E. Sanderson
8. Paul Shinn
9. Rick Schneider
10. Zina Itkin
11. Hui Guo
12. Min Shen
13. Carleen Klumpp-Thomas
14. Samuel G. Michael
15. Wei Zheng
16. Anton Simeonov
17. Matthew D. Hall

Reviewed by ScreenIT

Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration

1. Sebastian Fiedler
2. Sean R. A. Devenish
3. Alexey S. Morgunov
4. Alison Ilsley
5. Francesco Ricci
6. Marc Emmenegger
7. Vasilis Kosmoliaptsis
8. Elitza S. Theel
9. John R. Mills
10. Anton M. Sholukh
11. Adriano Aguzzi
12. Akiko Iwasaki
13. Andrew K. Lynn
14. Tuomas P. J. Knowles

Reviewed by ScreenIT

Structural basis for an unprecedented enzymatic alkylation in cylindrocyclophane biosynthesis

1. Nathaniel R Braffman
2. Terry B Ruskoski
3. Katherine M Davis
4. Nathaniel R Glasser
5. Cassidy Johnson
6. C Denise Okafor
7. Amie K Boal
8. Emily P Balskus

• Curated by eLife

  Evaluation Summary:

  The de novo crystal structure of the cyanobacterial enzyme CylK, which assembles cylindrocyclophane natural products, is reported. The substrate-binding site and critical catalytic residues were identified through a combination of anion soaking, mutagenesis, molecular dynamic simulations. The insights from this work are relevant in understanding biological Friedel-Crafts alkylation and also in enzyme engineering and catalyst designs. This is a very comprehensive study that provides new mechanistic insights for this enzyme and it will be of interest to all who are involved in enzyme engineering, catalyst design, and natural product discovery.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Cryo-EM structures reveal high-resolution mechanism of a DNA polymerase sliding clamp loader

1. Christl Gaubitz
2. Xingchen Liu
3. Joshua Pajak
4. Nicholas P Stone
5. Janelle A Hayes
6. Gabriel Demo
7. Brian A Kelch

• Curated by eLife

  Evaluation Summary:

  This work reports several cryoEM structures of clamp loader-sliding clamp complexes, which are required for DNA replication and repair in all domains of life, and is of interest to researchers studying DNA metabolism and motor proteins. The findings provide new insight into the mechanism of clamp loading and the mechanisms by which ligands affect the conformational dynamics of motor proteins to facilitate their reactions.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

A cryptic K48 ubiquitin chain binding site on UCH37 is required for its role in proteasomal degradation

1. Jiale Du
2. Sandor Babik
3. Yanfeng Li
4. Kirandeep K Deol
5. Stephen J Eyles
6. Jasna Fejzo
7. Marco Tonelli
8. Eric Strieter

• Curated by eLife

  Evaluation Summary:

  This study identifies a cryptic ubiquitin-binding site on the proteasome-associated deubiquitinase UCH37 and reveals that branched ubiquitin chains are bound and processed differently from mono-ubiquitin modifications. The authors use a variety of elegant biochemical and biophysical approaches to characterize this new binding site, and the conclusions are very well supported by the experimental data. These findings provide important new insights into the cleavage of branched ubiquitin chains during protein degradation by the 26S proteasome, therefore represent a critical advance to the ubiquitin-proteasome field and our understanding of how ubiquitin signaling regulates protein turnover in the cell, and will be of interest to a broad audience.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Histidine-rich protein 2: a new pathogenic factor of Plasmodium falciparum malaria

1. Takashi Iwasaki
2. Mayu Shimoda
3. Haru Kanayama
4. Tsuyoshi Kawano

Reviewed by Review Commons

Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance

1. Ala M. Shaqra
2. Sarah N. Zvornicanin
3. Qiu Yu J. Huang
4. Gordon J. Lockbaum
5. Mark Knapp
6. Laura Tandeske
7. David T. Bakan
8. Julia Flynn
9. Daniel N. A. Bolon
10. Stephanie Moquin
11. Dustin Dovala
12. Nese Kurt Yilmaz
13. Celia A. Schiffer

Reviewed by ScreenIT

Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19

1. Yuto Unoh
2. Shota Uehara
3. Kenji Nakahara
4. Haruaki Nobori
5. Yukiko Yamatsu
6. Shiho Yamamoto
7. Yuki Maruyama
8. Yoshiyuki Taoda
9. Koji Kasamatsu
10. Takahiro Suto
11. Kensuke Kouki
12. Atsufumi Nakahashi
13. Sho Kawashima
14. Takao Sanaki
15. Shinsuke Toba
16. Kentaro Uemura
17. Tohru Mizutare
18. Shigeru Ando
19. Michihito Sasaki
20. Yasuko Orba
21. Hirofumi Sawa
22. Akihiko Sato
23. Takafumi Sato
24. Teruhisa Kato
25. Yuki Tachibana

Reviewed by ScreenIT