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Characterization of HIV-2 Protease Structure by Studying Its Asymmetry at the Different Levels of Protein Description

Guillaume Ollitrault, Sandrine Fartek, Diane Descamps, Anne-Claude Camproux, Benoît Visseaux, Leslie Regad
2018 Symmetry  
In this study, we developed an in silico protocol to analyze and characterize the asymmetry of the unbound PR2 structure using three levels of protein description by comparing the conformation, accessibility  ...  HIV-2 protease (PR2) is a homodimer, which is an important target in the treatment of the HIV-2 infection.  ...  Acknowledgments: We thank Natacha Cerisier and Pierre Laville for proofreading the manuscript. Conflicts of Interest: The authors declare no conflict of interest.  ... 
doi:10.3390/sym10110644 fatcat:gjttaststbf57ctmoiapzsgu2a

Exploration of the Structural Asymmetry Induced by the Intrinsic Flexibility of HIV-2 Protease

Anne Badel, Laëtitia Breuil, Pierre Laville, Leslie Regad
2022 Symmetry  
HIV-2 protease (PR2) is a homodimer targeted by drugs in the treatment of HIV-2 infections. This dimer is often considered symmetric.  ...  This study presents the first analysis of the structural asymmetry of PR2 induced by its intrinsic flexibility.  ...  It is therefore important to better characterize the structural features of HIV-2 PR (PR2), as this protein has not been as thoroughly studied as HIV-1 protease (PR1).  ... 
doi:10.3390/sym14020362 fatcat:xtree6ldwvcwthnfudyep272km

Analysis of the HIV-2 protease's adaptation to various ligands: characterization of backbone asymmetry using a structural alphabet

Dhoha Triki, Mario Enrique Cano Contreras, Delphine Flatters, Benoit Visseaux, Diane Descamps, Anne-Claude Camproux, Leslie Regad
2018 Scientific Reports  
The HIV-2 protease (PR2) is a homodimer of 99 residues with asymmetric assembly and binding various ligands.  ...  We propose an exhaustive study of the local structural asymmetry between the two monomers of all available PR2 structures complexed with various inhibitors using a structural alphabet approach.  ...  We would like to thank Natacha Cerisier for critical reading of the manuscript. We also thank Sébastien Turpin for his help design Figure 2 .  ... 
doi:10.1038/s41598-017-18941-3 pmid:29335428 pmcid:PMC5768731 fatcat:2krmk52ymzg6hgzj7gix332ffa

Pentacycloundecane lactam vs lactone norstatine type protease HIV inhibitors: binding energy calculations and DFT study

Bahareh Honarparvar, Sachin A Pawar, Cláudio Nahum Alves, Jerônimo Lameira, Glenn EM Maguire, José Rogério A Silva, Thavendran Govender, Hendrik G Kruger
2015 Journal of Biomedical Science  
The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory.  ...  It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental  ...  Acknowledgements We thank the National Research Foundation, South Africa for financial support, UKZN and the CHPC ( for computational resources.  ... 
doi:10.1186/s12929-015-0115-5 pmid:25889635 pmcid:PMC4387594 fatcat:l5zxu5gztzgazdgqgtqluzovpu

INHIBITORS OF HIV-1 PROTEASE: A Major Success of Structure-Assisted Drug Design

Alexander Wlodawer, Jiri Vondrasek
1998 Annual Review of Biophysics and Biomolecular Structure  
Retroviral protease (PR) from the human immunodeficiency virus type 1 (HIV-1) was identified over a decade ago as a potential target for structure-based drug design. This effort was very successful.  ...  The techniques utilized in this remarkable example of structure-assisted drug design included crystallography, NMR, computational studies, and advanced chemical synthesis.  ...  The past eight years have seen a virtual explosion of crystallographic studies aimed at the characterization of the structures of HIV PR and of HIV PR/inhibitor complexes on an atomic level (note that  ... 
doi:10.1146/annurev.biophys.27.1.249 pmid:9646869 fatcat:c6ye3dazifbspk2azamvminzta

Structural Characterization of B and non-B Subtypes of HIV-Protease: Insights into the Natural Susceptibility to Drug Resistance Development

Mario Sanches, Sandra Krauchenco, Nadia H. Martins, Alla Gustchina, Alexander Wlodawer, Igor Polikarpov
2007 Journal of Molecular Biology  
To gain more insights into the structure and function of different variants of HIV proteases, we have determined a 2.1 Å structure of the native subtype F HIV-1 protease (PR) in complex with the protease  ...  Genomic differences between the subtypes give rise to sequence variations in the encoded proteins, including the HIV-1 protease.  ...  Results and Discussion Protease sequences The sequence alignment of the four HIV proteases studied by us is presented in Figure 1 .  ... 
doi:10.1016/j.jmb.2007.03.049 pmid:17467738 fatcat:ai4szg6drfctpc6yggsw3hkip4

Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease

John M. Louis, Julien Roche
2016 Journal of Molecular Biology  
This study highlights the malleability of retroviral protease folding pathways by illustrating how the selection of mutations under drug pressure remodels the free-energy landscape as a primary mechanism  ...  Lack of structural cooperativity was observed between regions located close to the active site, including the hinge and tip of the glycine-rich flaps, and the rest of the protein.  ...  This research was supported by the Intramural Research Program of the NIDDK, National Institutes of Health and the Intramural AIDS-Targeted Program of the Office of the Director, NIH.  ... 
doi:10.1016/j.jmb.2016.05.005 pmid:27170547 pmcid:PMC4905781 fatcat:fsh4xcbslbfqpbyxnlqe55swlq

Comparison of a retroviral protease in monomeric and dimeric states

Stanislaw Wosicki, Miroslaw Gilski, Helena Zabranska, Iva Pichova, Mariusz Jaskolski
2019 Acta Crystallographica Section D: Structural Biology  
At variance with the previous study, all of the new structures have the canonical dimeric form of retroviral proteases.  ...  Mason–Pfizer monkey virus (M-PMV) is unique among retroviruses as its protease is also stable in the monomeric form, as confirmed by an existing crystal structure of a 13 kDa variant of the protein (M-PMV  ...  Acknowledgements The diffraction data were collected on beamlines BL14.1 and BL14.2 of the BESSY II electron-storage ring operated by the Helmholtz-Zentrum Berlin (Mueller et al., 2015) .  ... 
doi:10.1107/s2059798319011355 pmid:31588922 fatcat:ygohm6cazrgrflgl5jaqdufx54

Dynamic electrophoretic fingerprinting of the HIV-1 envelope glycoprotein

Daniel J Stieh, Joshua L Phillips, Paul M Rogers, Deborah F King, Gianguido C Cianci, Simon A Jeffs, Sandrasegaram Gnanakaran, Robin J Shattock
2013 Retrovirology  
In this study, we explored the surface chemistry of HIV-1 Env constructs at a range of pH and salinities relevant to mucosal and systemic compartments through electrophoretic mobility (EM) measurements  ...  Interactions between the HIV-1 envelope glycoprotein (Env) and its primary receptor CD4 are influenced by the physiological setting in which these events take place.  ...  Initial manufacture of gp120/140 protein was supported by funding from the International Partnership for Microbicides (IPM).  ... 
doi:10.1186/1742-4690-10-33 pmid:23514633 pmcid:PMC3648349 fatcat:4r4a6f6wfzd3lpxgasvluxf644

Crystal structure of a complex of HIV-1 protease with a dihydroxyethylene-containing inhibitor: Comparisons with molecular modeling

Narmada Thanki, J.K. Mohana Rao, Stephen I. Foundling, Alexander Wlodawer, W. Jeffrey Howe, Joseph B. Moon, John O. Hui, Alfredo G. Tomasselli, Robert L. Heinrikson, Suvit Thaisrivongs
1992 Protein Science  
The structure of the complex has been refined to a crystallographic R factor of 0. I69 at 2.0 A resolution by using restrained least-squares procedures.  ...  [CH(OH)CH(OH)]Vam-Ile-Amp (U-75875), and its Ki for inhibition of the HIV-I protease is < I .O nM (Noa = I-naphthoxyacetyl, Hch = a hydroxy-modified form of cyclohexylalanine, Vam = a hydroxy-modified  ...  Maria Miller for sharing with us her unpublished, highly refined structure of the MVT-101 complex. We are indebted to Dr.  ... 
doi:10.1002/pro.5560010811 pmid:1304383 pmcid:PMC2142164 fatcat:phsylh73ofhbbljrpqpv7pd67y

Virus Maturation

David Veesler, John E. Johnson
2012 Annual Review of Biophysics  
The elaborate assembly and maturation pathway of HIV is discussed in contrast to the less sophisticated but highly efficient processes associated with togaviruses.  ...  The data support divergent evolution of noda, picorna and tetraviruses from a common ancestor and divergent evolution of alpha and flaviviruses from a common ancestor.  ...  Work in the lab of JEJ was supported by grants from the National Institutes of Health R37 GM034220, R01 GM054076 and R01 AI040101.  ... 
doi:10.1146/annurev-biophys-042910-155407 pmid:22404678 pmcid:PMC3607295 fatcat:ng2xo7eksjfm5bq64ybz22ovku

Three-dimensional solution structure of the HIV-1 protease complexed with DMP323, a novel cyclic urea-type inhibitor, determined by nuclear magnetic resonance spectroscopy

Toshimasa Yamazaki, Andrew P. Hinck, Yun-Xing Wang, Linda K. Nicholson, Dennis A. Torchia, Paul Wingfield, Stephen J. Stahl, Joshua D. Kaufman, Chong-Hwan Chang, Peter J. Domaille, Patrick Y.S. Lam
2008 Protein Science  
The latter structure is similar to the 1.8-A X-ray structure of the protease/DMP323 complex (Chang C H et al., 1995, Protein Science, submitted); the pairwise backbone RMSD calculated for the two structures  ...  The three-dimensional solution structure of the HIV-I protease homodimer, MW 22.2 kDa, complexed to a potent, cyclic urea-based inhibitor, DMP323, is reported.  ...  This work was supported by the AIDS Targeted Antiviral Program of the Office of the Director of the National Institutes of Health.  ... 
doi:10.1002/pro.5560050311 pmid:8868486 pmcid:PMC2143364 fatcat:oc734f2u5bbdxe36r5r54mx4jq

Comparing the Accumulation of Active- and Nonactive-Site Mutations in the HIV-1 Protease†

José C. Clemente, Rebecca E. Moose, Reena Hemrajani, Lisa R. S. Whitford, Lakshmanan Govindasamy, Robbie Reutzel, Robert McKenna, Mavis Agbandje-McKenna, Maureen M. Goodenow, Ben M. Dunn
2004 Biochemistry  
Protease inhibitor resistance still poses one of the greatest challenges in treating HIV.  ...  pretherapy structures in the Protein Data Bank.  ...  We also thank the following for gifts of the HIV protease inhibitors: Abbott Laboratories (ritonavir), Agouron Pharmaceuticals, now Pfizer, San Diego, CA (nelfinavir and AG1776), and Merck (indinavir).  ... 
doi:10.1021/bi049459m pmid:15379553 fatcat:mjjriexdzjegbl7ka26r7h2oay

A topological data analytic approach for discovering biophysical signatures in protein dynamics

Wai Shing Tang, Gabriel Monteiro da Silva, Henry Kirveslahti, Erin Skeens, Bibo Feng, Timothy Sudijono, Kevin K. Yang, Sayan Mukherjee, Brenda Rubenstein, Lorin Crawford, Petras J Kundrotas
2022 PLoS Computational Biology  
Identifying structural differences among proteins can be a non-trivial task.  ...  Statistically significant topological features are then projected back onto a user-selected representative protein structure, thus facilitating the visual identification of biophysical signatures of different  ...  Acknowledgments A majority of this research was conducted using computational resources and services at the Center for Computation and Visualization (CCV), Brown University.  ... 
doi:10.1371/journal.pcbi.1010045 pmid:35500014 pmcid:PMC9098046 fatcat:fmkw26c4sndd3a5o7ewifern2u

Intrinsically disordered protein

A.Keith Dunker, J.David Lawson, Celeste J Brown, Ryan M Williams, Pedro Romero, Jeong S Oh, Christopher J Oldfield, Andrew M Campen, Catherine M Ratliff, Kerry W Hipps, Juan Ausio, Mark S Nissen (+8 others)
2001 Journal of Molecular Graphics and Modelling  
Proteins can exist in a trinity of structures: the ordered state, the molten globule and the random coil.  ...  Disordered polyanion tails at the carboxy terminus bind many of these calcium ions, perhaps without adopting a unique structure.  ...  also Irwin Kuntz, Clare Woodward, Clay Bracken, and Richard Goldstein whose comments at the meeting helped improve our understanding of our own work.  ... 
doi:10.1016/s1093-3263(00)00138-8 pmid:11381529 fatcat:6uxu36wfgjaqfjb5seglqkn7n4
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