AK4 + Gp5G

AK4 + Gp5G

AK4 + Gp5G: Human Adenylate Kinase 4 in complex with diguanosine pentaphosphate
PDB Code: 2BBW
Adenylate kinases are essential for the maintenance of cellular energetic economy and are key enzymes in the synthesis, equilibration and regulation of nucleotides. AK’s catalyze nucleotide exchange (ATP + AMP <=> 2ADP or GTP + AMP <=> GDP + ADP) and facilitates transfer of both β- and γ-phosphoryls in ATP and other nucleotide substrates. In contrast to cytoplasmic AKs which participate in energy metabolism when local high energy phosphate levels are low, mitochondrial AKs (AK3 and AK4) function in the salvage pathway of AMP because this adenine nucleotide which accumulates in periods of energy demand cannot enter the mitochondrion and will be lost if not phosphorylated. It is likely that both mitochondrial AK’s use GTP as a substrate. However, the substrate specificity of human AK4 as well as its role in mitochondria remains to be clarified. The expression of AK4 mRNA is restricted in the brain hippocampus and cerebellum, olfactory neuroepithelium as well as liver. This result indicates that in contrast to AK3, AK4 acts on the specific mechanism of unusual energy metabolism rather than the control of homeostasis of the ADP pool ubiquitously.
It is therefore likely that the function of AK4 is rather the control of ATP/GTP metabolism for intracellular signal transduction, production of the neurotransmitters or the neurotrophic factors and neuroprotection in the case of ischemia. In order to address this question we determined the structure of AK4 in complex with a possible substrate analogue (Gp5G).

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