Biochemistry

Discovery of compounds that inhibit SARS-CoV-2 Mac1-ADP-ribose binding by high-throughput screening

1. Anu Roy
2. Yousef M. Alhammad
3. Peter McDonald
4. David K. Johnson
5. Junlin Zhuo
6. Sarah Wazir
7. Dana Ferraris
8. Lari Lehtiö
9. Anthony K.L. Leung
10. Anthony R. Fehr

Reviewed by ScreenIT

Flipped over U: structural basis for dsRNA cleavage by the SARS-CoV-2 endoribonuclease

1. Meredith N Frazier
2. Isha M Wilson
3. Juno M Krahn
4. Kevin John Butay
5. Lucas B Dillard
6. Mario J Borgnia
7. Robin E Stanley

Reviewed by ScreenIT

Design, Synthesis and Evaluation of Inhibitors of the SARS-CoV2 nsp3 Macrodomain

1. Lavinia M. Sherrill
2. Elva E. Joya
3. AnnMarie Walker
4. Anuradha Roy
5. Yousef M. Alhammad
6. Moriama Atobatele
7. Sarah Wazir
8. George Abbas
9. Patrick Keane
10. Junlin Zhuo
11. Anthony K.L. Leung
12. David K. Johnson
13. Lari Lehtiö
14. Anthony R. Fehr
15. Dana Ferraris

Reviewed by ScreenIT

Glutathione binding to the plant AtAtm3 transporter and implications for the conformational coupling of ABC transporters

1. Chengcheng Fan
2. Douglas C Rees

• Curated by eLife

  Evaluation Summary:

  Oxygen consumption in mitochondria by the respiratory chain leads to a major source of reactive oxygen species, and mitochondrial glutathione is an important line of defence against free radical production. The ABC transporter Atm3 exports oxidized glutathione from the mitochondria to help maintain a suitable reducing environment. Here, the authors have determined structure of Atm3 in multiple conformations by single-particle cryo EM and have revealed new insights into local changes coupled to substrate export of oxidised glutathione and ABC exporters in general. The work will be of interest to the mitochondrial biology and transporter communities.

  (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 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Structures of PKA–phospholamban complexes reveal a mechanism of familial dilated cardiomyopathy

1. Juan Qin
2. Jingfeng Zhang
3. Lianyun Lin
4. Omid Haji-Ghassemi
5. Zhi Lin
6. Kenneth J Woycechowsky
7. Filip Van Petegem
8. Yan Zhang
9. Zhiguang Yuchi

• Curated by eLife

  Evaluation Summary:

  Protein kinase A phosphorylation of phospholamban (PLN) is part of the "fight or flight" response, which ultimately increases the force of cardiac contraction. Mutations in PLN have been linked to familial dilated cardiomyopathy (DCM). Crystal structures of wild-type and mutant PLN in complex with the PKA catalytic domain provide insights into both the nature of the complex, and potential mechanisms by which DCM mutations may cause disease. This paper is of interest to scientists interested in the mechanism of substrate recruitment by protein kinases, and particularly those who have an interest in understanding the mechanism of mutations associated with dilated cardiomyopathy.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife

MicroRNA 3′-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position

1. Sean E McGeary
2. Namita Bisaria
3. Thy M Pham
4. Peter Y Wang
5. David P Bartel

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of interest to readers in the field of microRNA (miRNA) biology, particularly those interested in miRNA targeting. The authors interrogated non-canonical miRNA target recognition to a depth vastly exceeding any study to date. The results revealed unexpected, sequence-specific diversity in miRNA-targeting modes, providing new insights relevant for improved target prediction.

  (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 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Binding Interactions between RBD of Spike-Protein and Human ACE2 in Omicron variant

1. Bahaa Jawad
2. Puja Adhikari
3. Rudolf Podgornik
4. Wai-Yim Ching

Reviewed by ScreenIT

Distinct Core Glycan and O-Glycoform Utilization of SARS-CoV-2 Omicron Variant Spike Protein RBD Revealed by Top-Down Mass Spectrometry

1. David S. Roberts
2. Morgan Mann
3. Brad H. Li
4. Donguk Kim
5. Allan R. Brasier
6. Song Jin
7. Ying Ge

Reviewed by ScreenIT

Structural basis of dynamic P5CS filaments

1. Jiale Zhong
2. Chen-Jun Guo
3. Xian Zhou
4. Chia-Chun Chang
5. Boqi Yin
6. Tianyi Zhang
7. Huan-Huan Hu
8. Guang-Ming Lu
9. Ji-Long Liu

• Curated by eLife

  Evaluation Summary:

  This study describes the structures of filamentous forms of the enzyme P5CS from Drosophila, an enzyme important in the synthetic pathway for proline and ornithine. Three CryoEM experiments by the authors have resulted in structures of several apo and substrate-bound conformational states of the enzyme. The structures suggest that filamentation by P5CS may serve the purpose to facilitate the two-step enzymatic reaction by limiting the free diffusion of the reaction intermediate, the product of the first catalytic step and the substrate of the second, thereby increasing the reaction rate of the rate-limiting step (the second step) of the enzymatic reaction.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

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