Function(s) and Biological Relevance
Bap1, which is a protein found in bacterial biofilms in Vibrio Cholerae, plays a significant role in the medical world. It is involved in the disease progression of Cholera. Bap1 is composed of two main structural units which include the beta prism domain and the beta propeller domain. It's main role is to bind citrate and carbohydrates, which occurs in the binding pocket of the beta prism domain. The article analyzed takes a further look into the structural function of the protein and its significance to overall biofilm adhesion.
Broader Implications
It is important to study Bap1 because of its clinical relevance with Cholera. 1.3-4.0 million people are diagnosed with cholera each year on a world wide scale, with it taking 21,000-143,000 lives each year.[1] Cholera is transmitted indirectly through food and water that is contaminated with the Vibrio Cholerae bacteria. This is a huge issue considering that not everyone in the world has access to clean water. By understanding Bap1 and it's overall function, there is hope for figuring out how to break down it's bacterial biofilm and combat cholera.
Structural highlights and structure-function relationships
Secondary structure is important in Bap1. 6MLT is composed of two major domains, the beta-prism domain and the 8-bladed beta-propeller domain. Yellow represents the beta-helix, with pink showing the alpha-helix, white showing coils and loops, and turns in blue.
This image depicts the binding pocket at the top of the β-prism domain (the smaller complex). The image was put into spacefill so it is easier to see the pocket and identify steric significance. It is helpful to use a of the binding pocket in order to see where the citrate and sugars would bind.
One of the major functions of Bap1 is it's sugar binding properties. This image shows the binding pocket on the beta-prism, which is where carbohydrates bind. The molecule is shown in spacefill and is colored based on hydrophobicity. Hydrophilic residues are shown in blue, with hydrophobic residues in red, and non charged residues in white. Lys, which makes up a large part of the binding pocket is represented in lime green. The positively charged side chain on Lys makes it great for negatively charged sugars (and citrate) to bind to.
Asp 348, which is found on the beta-prism of Bap1, plays a crucial role in binding to citrate and carbohydrates. Mutation of aspartic acid to alanine results in a loss of function for Bap1. Since Ala has a much smaller side chain than Asp, it becomes too many Å away to interact.
There are six essential amino acids highlighted in the active site of 6MLT. They create interactions via hydrogen bonds or van der Waals in order to bind citrate and carbohydrates.
There are six essential amino acids involved in the binding of citrate. These six amino acids include Gly 344, Ala 345, Val 346, Lys 501, Asp 348, and His 500. Gly 344, Ala 345, Val 346, Lys 501 all interact with citrate via hydrogen bonding, while Asp 348 and His 500 interact via van der Waals interactions. The amino acids are shown in CPK to highlight properties that correspond with hydrogen bonding. Citrate molecules bind at the carbohydrate-binding site just like the sugars do.
There is a possibility that the ions found in the β-propeller play a role in structural stability, rather than a functional or enzymatic role. [2] The two types of ions found include sodium and calcium.
Bap1 has shown to contribute to the hydrophobicity of Vibrio Cholerae biofilms.[3] Pink represents the polar parts of Bap1, with gray showing the hydrohpbic components of Bap1. The red sections represent water molecules.
Energy Transformation
Since the overall purpose of Bap1 is to hold together biofilms, there are no energy transformations present.
