Question

Fibrinogen, a precursor to the bloodclot protein fibrin, contains tyrosine-O- sulfate. Propose an activated form of sulfate that could react in vivo with the aromatic hydroxyl group of a tyrosine residue in a protein to form tyrosine-O-sulfate.

Short answer

Phosphoadenosine phosphosulfate (PAPS) can act as an activated form of sulfate to react with tyrosine.

Step-by-step solution

Understand the Tyrosine-O-Sulfate Formation

The problem requires proposing a molecule that, when activated, can react with the hydroxyl group of the tyrosine residue in proteins to form tyrosine-O-sulfate. This process involves attaching a sulfate group onto the tyrosine's hydroxyl group (OH).

Identify the Activation Mechanism

For a sulfate group to attach to the tyrosine's hydroxyl group, it has to be activated. Sulfate esters are typically formed through nucleophilic attack on an activated sulfate compound. The activation often involves creating a good leaving group.

Propose an Activated Sulfate Form

An appropriate activated form of sulfate for the formation of a sulfate ester with tyrosine is the sulfate-phosphate compound, usually adenosine 5'-phosphosulfate (APS) or phosphoadenosine phosphosulfate (PAPS). These compounds contain sulfate groups activated by being bound to adenosine, making the sulfate group more electrophilic.

Explain the Reaction Mechanism

The aromatic hydroxyl group on tyrosine acts as a nucleophile. It attacks the electrophilic sulfur atom in the activated sulfate (such as PAPS), resulting in the formation of tyrosine-O-sulfate and the release of the phosphate or other leaving group. This type of reaction is catalyzed by specific enzymes in vivo.

Key concepts

Understanding Tyrosine-O-Sulfate

Tyrosine-O-sulfate is a post-translational modification, meaning it occurs after the initial protein synthesis. This transformation is important in biochemistry because it can alter a protein's function or stability. The modification involves attaching a sulfate group to the hydroxyl group of the tyrosine residue in a protein. By doing so, it introduces a sulfate group that enhances the protein's capacity for interactions. In many proteins, sulfate groups can increase binding affinity to ligands or receptors.

The process of adding a sulfate group to tyrosine, thereby forming tyrosine-O-sulfate, plays a crucial role in numerous biological processes, including blood clotting. A single protein might have more than one tyrosine residue, and not all of them may be sulfated. The specific sulfation of a particular tyrosine is often precise and critical for the protein's functioning. Understanding how tyrosine-O-sulfation occurs in proteins is vital for comprehending protein function and regulation in biochemical pathways.

The Role of Activated Sulfate Forms

For a sulfate group to successfully attach to a tyrosine residue in a protein, it must first be in an activated state. Activated sulfate forms play a critical role in this conversion process by providing a sulfate that is more reactive than its simple ionic form. These forms are essential for the sulfation reaction to occur efficiently.

In biochemical pathways, activated sulfate forms such as adenosine 5'-phosphosulfate (APS) or phosphoadenosine phosphosulfate (PAPS) are commonly involved. These compounds have a sulfate group linked to adenosine, which makes the sulfate group more electrophilic and prone to react with nucleophiles. The presence of adenosine also helps stabilize the sulfate in a form that can be effectively transferred to the tyrosine residue. This activation reduces the energy barrier for the reaction, allowing it to occur under physiological conditions.

Formation and Significance of Sulfate Esters

Sulfate esters are chemical compounds resulting from the reaction between a sulfate group and a hydroxyl group, such as that found on a tyrosine residue. In forming a sulfate ester, the hydroxyl group on tyrosine acts as a nucleophile and attacks the activated sulfate form at the sulfur atom. This forms a covalent bond, resulting in the tyrosine-O-sulfate ester.

The formation of sulfate esters is an essential reaction in many biological systems, serving in processes such as hormone activation, signal transduction, and structural modification of proteins. By converting tyrosine into its sulfated form, proteins can exhibit altered binding properties and enhanced stability. This biochemical transformation is crucial for maintaining cellular communication and function, especially in systems like coagulation and immune response.

Moreover, enzymes in an organism's body facilitate the formation of sulfate esters, ensuring the reaction proceeds at a pace compatible with life processes. Understanding sulfate esters is important for biochemists who design drugs and treatments influencing these pathways.