Biochemistry

Zinc pyrithione is a potent inhibitor of PL ^Pro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication

1. Jerneja Kladnik
2. Ana Dolinar
3. Jakob Kljun
4. David Perea
5. Judith Grau-Expósito
6. Meritxell Genescà
7. Marko Novinec
8. Maria J. Buzon
9. Iztok Turel

Reviewed by ScreenIT

Inhibitory proteins block substrate access by occupying the active site cleft of Bacillus subtilis intramembrane protease SpoIVFB

1. Sandra Olenic
2. Lim Heo
3. Michael Feig
4. Lee Kroos

• Curated by eLife

  Evaluation Summary:

  A member of a large class of metalloproteases with representatives in mammals as well as bacteria, its status as a multipass membrane protein has made illuminating the molecular basis of SpoIVFB inhibition challenging. In this study, Olenic and colleagues combine genetics, cross-linking, and co-evolutionary analysis to develop a structural model of interaction between SpoIVFB and its inhibitors SpoIVFA and BofA. Given the conservation and importance of this family of metalloproteases, this work should have broad impact, influencing our understanding of the regulation of this class of proteins across the tree of life.

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

Reviewed by eLife

Emergent properties of a mitotic Kif18b-MCAK-EB network

1. Toni McHugh
2. Julie P.I. Welburn

• Curated by eLife

  Evaluation Summary:

  The authors investigate the mechanisms underlying the regulation of microtubule dynamics and length regulation in cells. Understanding how microtubule-binding proteins synergize to affect microtubule behavior is important, and resolving the seemingly contradictory effects of Kif18a on microtubules in mitotic cells vs. in vitro microtubule assays is a worthy endeavor. A major conclusion is that on dynamic microtubules, combining EB3, MCAK, and Kif18b increases microtubule catastrophe compared to other single or double protein combinations. This is in principle a new and interesting finding, but additional evidence would help to more strongly support this conclusion.

  (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

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