8CRG

E. coli adenylate kinase in complex with two ADP molecules as a result of enzymatic AP4A hydrolysis

Summary for 8CRG

• Entry DOI: 10.2210/pdb8crg/pdb
• Descriptor: Adenylate kinase, ADENOSINE-5'-DIPHOSPHATE, 3[N-MORPHOLINO]PROPANE SULFONIC ACID, ... (4 entities in total)
• Functional Keywords: phosphotransferase, energy metabolism, ap4a hydrolysis, potential moonlighting protein, transferase
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 2
• Total formula weight: 49158.12

Authors

Oelker, M.,Tischlik, S.,Wolf-Watz, M.,Sauer-Eriksson, A.E. (deposition date: 2023-03-08, release date: 2023-06-14, Last modification date: 2023-10-25)

Primary citation

Tischlik, S.,Oelker, M.,Rogne, P.,Sauer-Eriksson, A.E.,Drescher, M.,Wolf-Watz, M.
Insights into Enzymatic Catalysis from Binding and Hydrolysis of Diadenosine Tetraphosphate by E. coli Adenylate Kinase.
Biochemistry, 62:2238-2243, 2023

PubMed Abstract: Adenylate kinases play a crucial role in cellular energy homeostasis through the interconversion of ATP, AMP, and ADP in all living organisms. Here, we explore how adenylate kinase (AdK) from interacts with diadenosine tetraphosphate (AP4A), a putative alarmone associated with transcriptional regulation, stress, and DNA damage response. From a combination of EPR and NMR spectroscopy together with X-ray crystallography, we found that AdK interacts with AP4A with two distinct modes that occur on disparate time scales. First, AdK dynamically interconverts between open and closed states with equal weights in the presence of AP4A. On a much slower time scale, AdK hydrolyses AP4A, and we suggest that the dynamically accessed substrate-bound open AdK conformation enables this hydrolytic activity. The partitioning of the enzyme into open and closed states is discussed in relation to a recently proposed linkage between active site dynamics and collective conformational dynamics.

PubMed: 37418448
DOI: 10.1021/acs.biochem.3c00189

Experimental method

X-RAY DIFFRACTION (1.49 Å)