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Deciphering the catalysis-associated conformational changes of human adenylate kinase 1 with single-molecule spectroscopy


, : Deciphering the catalysis-associated conformational changes of human adenylate kinase 1 with single-molecule spectroscopy. Journal of Physical Chemistry. B 117(45): 13947-13955

Human adenylate kinase isoenzyme 1 (AK1) is the key enzyme in maintaining the cellular energy homeostasis. The catalysis-associated conformational changes of AK1 involve large-amplitude rearrangements. To decipher the conformational changes of AK1 at the single-molecule level, we tagged AK1 with two identical fluorophores, one near the substrate-binding site and the other at the boundary of the core domain. We found that magnesium ion binding to AK1 increases the structural heterogeneity of AK1, whereas ADP binding reduces the structural heterogeneity. We exploited the hidden Markov model to extract the underlying catalysis-associated conformational dynamics and determined thermodynamic parameters of the multiple catalytic pathways. The third-order correlation difference calculated from photon fluctuation traces reveals the irreversible nature of the conformational motions, suggesting that single-molecule AK1 is in a nonequilibrium steady state. This discovery offers a fresh viewpoint to look into the molecular mechanisms of cellular biochemistry.

US$19.90

PMID: 24134437

DOI: 10.1021/jp4019537


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Boersma M., 1989: On the growth of cuneate leaves in Sphenophyllum. Carinthia II 99(1): 111-125

Calnan, C.D.; Sarkany, I., 1958: Contact dermatitis from neomycin. British Journal of Dermatology 70(12): 435-445

Chen-Morris, R., 2009: From emblems to diagrams: Kepler's new pictorial language of scientific representation. Kepler's treatise on optics of 1604 furnished, along with technical solutions to problems in medieval perspective, a mathematically-based visual language for the observation of nature. This language, based on Kepler's theory of retinal p...

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Breitmaier E.; Voelter W., 1973: Studies of configuration and conformation of adenosine analogues with carbon 13 resonance. Tetrahedron 29(1): 227-232

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Spaeth, G.L., 1994: Health-care reform issues and role of donors. Lancet 344(8929): 1090-1090

Brito, E.; Verocai, I., 1999: Environmental impact assessment in South and Central America. Petts, J [Editor] Handbook of environmental impact assessment, Vol 2 Environmental impact assessment in practice: Impact and limitations 183-202

Prunier A.; Caritez J.C.; Bonneau M., 1987: Genital tract development and 5 alpha androstenone concentration pattern during growth in male and female pigs of european and chinese breeds. Genital tract development in male and female pigs of European Large White (LW) or Chinese Mei-Shan (MS) breeds was studied at various ages during sexual development. Fat androstenone level in fatty tissue was measured in males of both breeds. Repr...