Article
Multidisciplinary Sciences
Fumiaki Ito, Ana L. Alvarez-Cabrera, Shiheng Liu, Hanjing Yang, Anna Shiriaeva, Z. Hong Zhou, Xiaojiang S. Chen
Summary: Human APOBEC3G (A3G) is a virus restriction factor that inhibits HIV-1 replication and triggers lethal hypermutation. HIV-1 viral infectivity factor (Vif) hijacks a cellular E3 ubiquitin ligase complex to target A3G and evade immune response. Understanding the molecular mechanism of this interaction is crucial for developing antiretroviral therapeutics.
Review
Biochemistry & Molecular Biology
Atanu Maiti, Shurong Hou, Celia A. Schiffer, Hiroshi Matsuo
Summary: APOBEC3 enzymes play a crucial role in regulating antiviral response in HIV, but may also contribute to diversity in cancer. Recent studies have revealed the diversity of epitopes involved in APOBEC3 binding to nucleic acids, highlighting the importance of the interplay between these interactions in uncovering how APOBEC3s recognize and process their substrates.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Camille Libre, Tanja Seissler, Santiago Guerrero, Julien Batisse, Cedric Verriez, Benjamin Stupfler, Orian Gilmer, Romina Cabrera-Rodriguez, Melanie M. Weber, Agustin Valenzuela-Fernandez, Andrea Cimarelli, Lucie Etienne, Roland Marquet, Jean-Christophe Paillart
Summary: The HIV-1 Vif protein decreases the expression of cellular restriction factors APOBEC3G, A3F, A3D, and A3H, which inhibit viral replication. The translation of A3G is regulated by a conserved uORF in the 5' untranslated region of its mRNA. This uORF is also important for Vif-mediated translation inhibition and redirection of A3G mRNA into stress granules.
Review
Microbiology
Daniel J. Salamango, Reuben S. Harris
Summary: Accessory proteins like Vif play a crucial role in distinguishing primate immunodeficiency viruses such as HIV-1, by not only antagonizing APOBEC3 enzymes but also triggering cell cycle arrest through the degradation of PPP2R5 proteins. These functions of Vif have opened up new avenues for accessory protein research and potential opportunities for drug development.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Xinxin Zhong, Ronghua Luo, Guoyi Yan, Kai Ran, Huifang Shan, Jie Yang, Yuanyuan Liu, Su Yu, Chunlan Pu, Yongtang Zheng, Rui Li
Summary: Through the optimization of the Vif antagonist ring C, compound 6m was discovered to exhibit stronger antiviral activity compared to 2, as well as effectively suppress the replication of various drug-resistant HIV strains, making it a more potent candidate for treating AIDS.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ryan S. Ramos, Rosivaldo S. Borges, Joao S. N. de Souza, Inana F. Araujo, Mariana H. Chaves, Cleydson B. R. Santos
Summary: This study aimed to identify potential inhibitors for SARS-CoV-2 ACE2 receptors and investigate their mechanism of action using molecular modeling and theoretical determination of biological activity. Through virtual screening and docking studies, several molecules with antiviral potential were identified. The pharmacokinetic and toxicological studies showed these molecules to have low toxicity and good bioavailability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xiaoxuan Yan, Chao Chen, Chunxi Wang, Wenxian Lan, Jianguo Wang, Chunyang Cao
Summary: APOBEC3G is a member of the cytosine deaminase family with innate immune functions. This research screened and identified five asymmetrical disulfides that inhibit the interaction between A3G and Vif, restoring A3G expression and opening up possibilities for the discovery of new anti-HIV drugs.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Biochemical Research Methods
Robyn M. Kaake, Ignacia Echeverria, Seung Joong Kim, John Von Dollen, Nicholas M. Chesarino, Yuqing Feng, Clinton Yu, Hai Ta, Linda Chelico, Lan Huang, John Gross, Andrej Sali, Nevan J. Krogan
Summary: The study introduced a pipeline for structural characterization of host-pathogen protein complexes using integrative structure modeling based on chemical cross-links and residue-protein contacts inferred from mutagenesis studies. The approach was applied to determine the structure of the (A3G-Vif-CRL5-CBF beta) complex, revealing insights into the interactions within the complex. The model created using this approach was validated and used to rationalize previous structural, mutagenesis, and functional data related to the A3G-Vif interface.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Review
Virology
Benjamin Stupfler, Cedric Verriez, Sarah Gallois-Montbrun, Roland Marquet, Jean-Christophe Paillart
Summary: The ubiquitin-proteasome system plays a crucial role in normal cell physiology and during viral infections. HIV-1 viral infectivity factor (Vif) has been shown to counteract cellular deaminases by recruiting E3-ubiquitin ligase complex, leading to their polyubiquitination and degradation. Research on the degradation-independent inhibition of A3s by Vif remains limited, but it has been shown to impede A3s through other processes.
Article
Biochemistry & Molecular Biology
Kailash Chand, Muneesh Kumar Barman, Payel Ghosh, Debashis Mitra
Summary: The HSP40/DNAJ family of proteins is highly diverse and contains around 49 isoforms in humans. Some of these isoforms have been shown to play functional roles in the pathogenesis of viruses, including HIV-1. Our study found that several isoforms of HSP40 were significantly modulated during HIV-1 infection in T cells at the mRNA level. We investigated the biological role of these modulated isoforms and found that certain isoforms positively regulate virus replication, while others negatively regulate it. Additionally, we discovered that one isoform, DNAJB8, specifically regulates the infectivity of progeny virions by downregulating the Vif protein.
Article
Biology
Md Minhas Hossain Sakib, Aktiya Anjum Nishat, Mohammad Tarequl Islam, Mohammad Abu Raihan Uddin, Md Shahriar Iqbal, Farhan Fuad Bin Hossen, Mohammad Imran Ahmed, Md Samiul Bashir, Takbir Hossain, Umma Sumia Tohura, Saiful Islam Saif, Nabilah Rahman Jui, Mosharaf Alam, Md Aminul Islam, Md Mehadi Hasan, Md Abu Sufian, Md Ackas Ali, Rajib Islam, Mohammed Akhter Hossain, Mohammad A. Halim
Summary: The study found that peptides may be effective drugs against SARS-CoV-2, with AVP1795 identified as the most promising candidate that could inhibit the recognition of SARS-CoV-2 by hACE2 as predicted by molecular dynamics simulation. Peptide-protein interactions were substantially influenced by hydrogen bonding and hydrophobic interactions.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
A. S. Tikhonov, R. R. Mintaev, D. V. Glazkova, E. V. Bogoslovskaya, G. A. Shipulin
Summary: The mechanisms for protecting the human body from viral or bacterial agents are diverse. APOBEC3 family proteins, including APOBEC3G, play an important role in congenital immunity and can protect against HIV. However, viral protein Vif counteracts the action of APOBEC3G by promoting its degradation. This review discusses potential strategies to enhance the anti-HIV activity of APOBEC3G and utilize modified APOBEC3G in HIV gene therapy.
Article
Biochemistry & Molecular Biology
Gyles E. Cozier, Emma C. Newby, Sylva L. U. Schwager, R. Elwyn Isaac, Edward D. Sturrock, K. Ravi Acharya
Summary: This study investigates the two isoforms of human angiotensin I-converting enzyme (ACE) and their different substrate specificities and structural features. By studying the structural characteristics of each domain, more specific and potent ACE inhibitors can be designed to reduce side effects and potentially be used clinically.
Article
Biochemistry & Molecular Biology
Kyle S. Gregory, Gyles E. Cozier, Sylva L. U. Schwager, Edward D. Sturrock, K. Ravi Acharya
Summary: This study reports the structural basis of domain-specific inhibition of angiotensin-1-converting enzyme (ACE) by lactotripeptides Val-Pro-Pro and Ile-Pro-Pro. The milk-derived lactotripeptides LPP and VPP have shown promising results in reducing hypertension by inhibiting the N- and C-domain of ACE. The resolution of two X-ray crystal structures and kinetic analysis provide important insights into the molecular interactions underlying this inhibition.
Article
Virology
Nicholas M. Chesarino, Michael Emerman
Summary: APOBEC3G (A3G) is an antiviral protein that restricts retroviruses like HIV. HIV-1 Vif has evolved to antagonize A3G. Two rapidly evolving sites in A3G act as a barrier to cross-species transmission of retroviruses. This study explores the evolutionary space of A3G at these sites to understand the advantage gained by HIV-1 Vif in its arms race with A3G.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ponnandy Prabhu, Shivender M. D. Shandilya, Elena Britan-Rosich, Adi Nagler, Celia A. Schiffer, Moshe Kotler
Article
Biochemistry & Molecular Biology
Takahide Kouno, Elizabeth M. Luengas, Megumi Shigematsu, Shivender M. D. Shandilya, JingYing Zhang, Luan Chen, Mayuko Hara, Celia A. Schiffer, Reuben S. Harris, Hiroshi Matsuo
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2015)
Article
Multidisciplinary Sciences
Sivakumar Boopathy, Tania V. Silvas, Maeve Tischbein, Silvia Jansen, Shivender M. Shandilya, Jill A. Zitzewitz, John E. Landers, Bruce L. Goode, Celia A. Schiffer, Daryl A. Bosco
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Biochemistry & Molecular Biology
Markus-Frederik Bohn, Shivender M. D. Shandilya, Tania V. Silvas, Ellen A. Nalivaika, Takahide Kouno, Brian A. Kelch, Sean P. Ryder, Nese Kurt-Yilmaz, Mohan Somasundaran, Celia A. Schiffer
Article
Biochemistry & Molecular Biology
Shivender Shandilya, Nese Kurt Yilmaz, Andrew Sadowski, Ejemel Monir, Zachary A. Schiller, William D. Thomas, Mark S. Klempner, Celia A. Schiffer, Yang Wang
JOURNAL OF MOLECULAR RECOGNITION
(2017)
Article
Multidisciplinary Sciences
Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender M. D. Shandilya, Markus F. Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo, Celia A. Schiffer
NATURE COMMUNICATIONS
(2017)
Article
Biochemistry & Molecular Biology
Ming Li, Shivender M. D. Shandilya, Michael A. Carpenter, Anurag Rathore, William L. Brown, Angela L. Perkins, Daniel A. Harki, Jonathan Solberg, Derek J. Hook, Krishan K. Pandey, Michael A. Parniak, Jeffrey R. Johnson, Nevan J. Krogan, Mohan Somasundaran, Akbar Ali, Celia A. Schiffer, Reuben S. Harris
ACS CHEMICAL BIOLOGY
(2012)
Meeting Abstract
Biophysics
Karen Mruk, Shivender M. D. Shandilya, Robert O. Blaustein, Celia A. Schiffer, William R. Kobertz
BIOPHYSICAL JOURNAL
(2012)
Article
Biochemistry & Molecular Biology
Michael A. Carpenter, Ming Li, Anurag Rathore, Lela Lackey, Emily K. Law, Allison M. Land, Brandon Leonard, Shivender M. D. Shandilya, Markus-Frederik Bohn, Celia A. Schiffer, William L. Brown, Reuben S. Harris
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Multidisciplinary Sciences
Karen Mruk, Shiven M. D. Shandilya, Robert O. Blaustein, Celia A. Schiffer, William R. Kobertz
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2012)
Article
Biochemistry & Molecular Biology
Shivender M. D. Shandilya, Madhavi N. L. Nalam, Ellen A. Nalivaika, Phillip J. Gross, Johnathan C. Valesano, Keisuke Shindo, Ming Li, Mary Munson, William E. Royer, Elena Harjes, Takahide Kono, Hiroshi Matsuo, Reuben S. Harris, Mohan Somasundaran, Celia A. Schiffer
Article
Biochemistry & Molecular Biology
Markus-Frederik Bohn, Shivender M. D. Shandilya, John S. Albin, Takahide Kouno, Brett D. Anderson, Rebecca M. McDougle, Michael A. Carpenter, Anurag Rathore, Leah Evans, Ahkillah N. Davis, JingYing Zhang, Yongjian Lu, Mohan Somasundaran, Hiroshi Matsuo, Reuben S. Harris, Celia A. Schiffer
Article
Virology
Shivender M. D. Shandilya, Markus-Frederik Bohn, Celia A. Schiffer
Article
Biology
Carina C. Clingman, Laura M. Deveau, Samantha A. Hay, Ryan M. Genga, Shivender M. D. Shandilya, Francesca Massi, Sean P. Ryder