Multidrug Transporter Sav1866
This Jmol Exploration was created using the Jmol Exploration Webpage Creator from the MSOE Center for BioMolecular Modeling.
This ABC transporter protein is found in the bacteria Staphyloccus aureus. This is a membrane protein that is responsible for transporting a variety of substrates across the membranes of cells and organelles. In bacteria, this protein is associated with resistance to drugs and antibiotics. In this tutorial, you will explore the structure of the ABC transporter Sav1866 as well as learn how its structure is related to its function as a multidrug resistance transporter.
The Sav1866 protein is composed of 578 amino acid residues in its polypeptide chain. These amino acids are held together by covalent bonds called peptide bonds.
Primary StructureThe secondary structure of the Sav1866 protein consists of alpha helices and beta pleated sheets. There are 32 alpha helices that contain 638 amino acid residues and 12 beta pleated sheets that contain 55 amino acid residues. In the Jmol structure, the alpha helices are shown as ribbons and the beta pleated sheets are shown as strands. The secondary structure also contains a supersecondary motif, called an alpha barrel. This structure is composed of the alpha helices that point downward near the bottom of the protein. We will review this structure later in this tutorial as it has a great deal of importance when it come to the function of this protein as an ABC transporter.
Secondary StructureThe tertiary structure of Sav1866 is globular. This structure is caused interactions between the side chains of the amino acids. These interactions include the following. Hydrophobic interactions in which the side chains that are nonpolar are facing toward the inside of the protein where they are not exposed to water. Salt bridges in which polar acid amino acids interact with polar basic side chains. Hydrogen bonding and dipole-dipole interactions in which polar side chains interact with each other. Finally, there are disulfide bonds, in which the sulfur in side chains interacts with each other. All of these various interactions are present in the tertiary structure of Sav1866.
Tertiary StructureThe quaternary structure of Sav1866 is a dimer. This is because it consists of two units; A and B.
As stated at the beginning of this tutorial, Sav1866 it s transmembrane protein that is classified as an ABC transporter protein. These proteins function to translocate various substrates across the membranes of cells and organelles. Sav1866 has four very important conformations. The first group is two transmembrane domains(TMDs) which function to provide a translocation pathway. The other group is two cytoplasmic, water-exposed nucleotide-binding domains(NBDs) that function of bind and hydrolyze ATP to ADP. The mechanism behind how this protein works is a coupling reaction between the hydrolysis of ATP and the movement of the substrate into or out of the translocation channel. Once a substrate enters the channel, it is ready for translocation. This occurs when ATP is bound and hydrolyzed to ADP because the energy produced in the hydrolysis is used the move the substrate. ABC transporter proteins are known to contribute to drug and antibiotic resistance for this reason. For example, if an antibiotic has made its way into the cell of a Staphyloccus aureus, it is intended to damage the cell to the point of death. However, if it makes its way into the translocation channel of Sav1866 and ATP is bound and hydrolyzed to ADP, then the antibiotic can be moved out of the cell.
Dawson, R., Locher, K. (2007). Structure of the multidrug ABC transporter Sav1866 from Staphyloccocus aureus in complex with AMP-PNP. Institute of Molecular Biology and Biophysics. pp 935-938.