Related Experiment Video

Updated: Feb 1, 2026

Visualization of HIV-1 Gag Binding to Giant Unilamellar Vesicle GUV Membranes
08:21

Visualization of HIV-1 Gag Binding to Giant Unilamellar Vesicle GUV Membranes

Published on: July 28, 2016

9.4K

MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat

Michael D Purdy1, Dan Shi2, Jakub Chrustowicz1

  • 1Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908.

Proceedings of the National Academy of Sciences of the United States of America
|December 12, 2018
PubMed

Insights

Maturation inhibitor bevirimat (BVM) stabilizes HIV-1 Gag protein assembly by interacting with the CA-SP1 junction. This structural insight from MicroED aids in developing new HIV maturation inhibitors for drug discovery.

Area of Science:

  • Structural Biology
  • Virology
  • Drug Discovery

Background:

  • HIV-1 Gag polyprotein processing is crucial for viral maturation and infectivity.
  • Cleavage at the CA-SP1 junction is a key step in HIV particle assembly.
  • Maturation inhibitors target this late stage of the viral lifecycle.

Purpose of the Study:

  • To elucidate the binding interactions of bevirimat (BVM) with the HIV-1 Gag CTD-SP1 construct.
  • To determine the structural basis for BVM's mechanism of action.
  • To showcase MicroED for structure-based drug design.

Main Methods:

  • Microcrystal Electron Diffraction (MicroED) was used to analyze 3D microcrystals.
  • Structures were determined for a CTD-SP1 Gag construct with and without bound BVM.
  • High-resolution structural data (2.9 Å) was obtained.

Main Results:

  • A single BVM molecule was observed to stabilize the six-helix bundle structure.
  • Bevirimat engages in both electrostatic and hydrophobic interactions within the binding site.
  • The dimethylsuccinyl moiety and pentacyclic triterpenoid ring of BVM are key interaction points.

Conclusions:

  • Bevirimat inhibits HIV-1 maturation by stabilizing the Gag protein structure.
  • Understanding these interactions informs the design of novel maturation inhibitors.
  • MicroED is a powerful tool for structure-based drug design in virology.
Keywords:
GagHIV-1cryoEMdrug discoverymaturation inhibitors

More Related Videos

A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses14:23

A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses

Published on: August 31, 2014

16.1K
A High-throughput Cre-Lox Activated Viral Membrane Fusion Assay to Identify Inhibitors of HIV-1 Viral Membrane Fusion07:22

A High-throughput Cre-Lox Activated Viral Membrane Fusion Assay to Identify Inhibitors of HIV-1 Viral Membrane Fusion

Published on: August 14, 2018

7.0K

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
15.0K
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.2K
Factors Affecting Protein-Drug Binding: Drug Interactions01:23

Factors Affecting Protein-Drug Binding: Drug Interactions

Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
602
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.1K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.3K