About Adenylate kinase / ADK:
Adenylate kinase is often referred to as the ADK protein. This protein is a phosphotransferase enzyme with catalytic properties. It helps catalyze the interconversion of adenine nucleotides - this includes ATP, ADP, and AMP. In essence, it will offer continuous monitoring of the phosphate nucleotide levels inside of a cell. Therefore, ADK is seen to play one of the critical roles in cellular energy homeostasis.
Adenylate kinase Structure
Adenylate kinase is considered a signal-transducing protein. As a consequence, this affects the way it is structured. It has a balance between conformations, which regulates protein activity. When it isn’t bound to anything, ADK has a locally unfolded state.
Interestingly, studies have shown that ADK protein actually has three different structures. There’s the open structure, the closed structure, and the CORE structure. As such, it is considered to be a very flexible protein. What’s more, ADK is also said to have a crystal structure.
ADK Mechanism & Interactions
Phosphoryl transfer is only possible when the ‘open lid’ of ADK has closed. From here, water molecules can’t get in, which helps move different substrates closer to one another. In turn, this reduces the energy barrier for the nucleophilic attack by the y-phosphoryl group of ATP upon the a-phosphoryl of AMP.
If we look at the structure of the ADK enzyme present in E. coli - with inhibitor Ap5A - then we notice that the Arg88 residue connects to the Ap5A. From here, the mutation of R88G leads to a near 100% loss of catalytic activity for this specific enzyme. As such, it points to the idea that this residue is intrinsically linked to phosphoryl transfer.
On the adenose region of ADK, we have the highly conserved Arg119 residue. Ere, this residue sandwiches the adenine in the active binding site. By doing this, it’s believed that the promiscuity of these enzymes in how they accept other NTP’s is related to the interactions on the base of the ATP binding pocket.
Adenylate kinase Function
There are two critical functions of adenylate kinase. Firstly, we have metabolic monitoring. This refers to a cells ability to measure energetic levels with a method to monitor metabolic processes. ADK continuously monitors ATP, ADP, AMP - and other adenyl phosphates. By doing this, it helps regulate the amount of energy expended at the cellular level. When various metabolic stresses alter the energy levels, ADK can then generate AMP to help control things. ADK activity is commonly influenced by the following; exercise, stress, hormone level alterations, and diet.
The second function is called ADK shuttle. Effectively, adenylate kinase is a crucial figure in myofibrillar and mitochondrial areas of the cell. As such, it makes two high-energy phosphoryl of ATP, which can be moved between different adenine nucleotide molecules. Simply put; ADK acts as a shuttle that transfers ATP to the high energy consumption sites, then gets rid of AMP generated through these reactions. This process also leads to changes in the local intracellular metabolic flux - but it doesn’t create any alterations in global changes in metabolic concentrations. ADK shuttle is a function that’s imperative for general homeostasis of a cell.