7X7S

Solution structure of human adenylate kinase 1 (hAK1)

Summary for 7X7S

• Entry DOI: 10.2210/pdb7x7s/pdb
• Descriptor: Adenylate kinase isoenzyme 1 (1 entity in total)
• Functional Keywords: adenylate kinase, adp, atp, lid domain, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 22079.33

Authors

Zhang, H. (deposition date: 2022-03-10, release date: 2022-05-11, Last modification date: 2024-05-15)

Primary citation

Guo, C.,Zhang, H.,Lin, W.,Chen, H.,Chang, T.,Wu, Z.,Yu, J.,Lin, D.
ADP-Induced Conformational Transition of Human Adenylate Kinase 1 Is Triggered by Suppressing Internal Motion of alpha 3 alpha 4 and alpha 7 alpha 8 Fragments on the ps-ns Timescale.
Biomolecules, 12:-, 2022

PubMed Abstract: Human adenylate kinase 1 (AK1) plays a vital role in the energetic and metabolic regulation of cell life, and impaired functions of AK1 are closely associated with many diseases. In the presence of Mg ions, AK1 in vivo can catalyze two ADP molecules into one ATP and one AMP molecule, activating the downstream AMP signaling. The ADP-binding also initiates AK1 transition from an open conformation to a closed conformation. However, how substrate binding triggers the conformational transition of AK1 is still unclear, and the underlying molecular mechanisms remain elusive. Herein, we determined the solution structure of apo-AK1 and its key residues for catalyzing ADP, and characterized backbone dynamics characteristics of apo-AK1 and AK1-Mg-ADP complex (holo-AK1) using NMR relaxation experiments. We found that ADP was primarily bound to a cavity surrounded by the LID, NMP, and CORE domains of AK1, and identified several critical residues for AK1 catalyzing ADP including G16, G18, G20, G22, T39, G40, R44, V67, D93, G94, D140, and D141. Furthermore, we found that apo-AK1 adopts an open conformation with significant ps-ns internal mobility, and Mg-ADP binding triggered conformational transition of AK1 by suppressing the ps-ns internal motions of αα in the NMP domain and αα in the LID domain. Both αα and αα fragments became more rigid so as to fix the substrate, while the catalyzing center of AK1 experiences promoted µs-ms conformational exchange, potentially facilitating catalysis reaction and conformational transition. Our results provide the structural basis of AK1 catalyzing ADP into ATP and AMP, and disclose the driving force that triggers the conformational transition of AK1, which will deepen understanding of the molecular mechanisms of AK1 functions.

PubMed: 35625598
DOI: 10.3390/biom12050671

Experimental method

SOLUTION NMR