Tracking the ATP-binding response in adenylate kinase in real time

Orädd, Fredrik; Ravishankar, Harsha; Goodman, Jack; Rogne, Per; Backman, Lars; Duelli, Annette; Pedersen, Martin Nors; Levantino, Matteo; Wulff, Michaël; Wolf‐Watz, Magnus; Andersson, Magnus

doi:10.1126/sciadv.abi5514

Cited by 26 publications

(15 citation statements)

References 88 publications

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“…Adenylate kinase (AdK), which catalyzes the phosphoryl transfer reaction ATP + AMP ⇌ ADP + ADP, has been widely used as a model system to study the interplay between conformational motions and enzymatic catalysis both experimentally and computationally. − This enzyme is composed of three domains, i.e., the CORE domain, the LID domain (ATP binding site), and the NMP domain (AMP binding site) (Figure a and b). The catalytic cycle of AdK involves conformational transitions between a closed conformation and an open conformation.…”

Section: Introductionmentioning

confidence: 99%

Role of Repeated Conformational Transitions in Substrate Binding of Adenylate Kinase

Scheerer

Haran

et al. 2022

J. Phys. Chem. B

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The catalytic cycle of the enzyme adenylate kinase involves large conformational motions between open and closed states. A previous single-molecule experiment showed that substrate binding tends to accelerate both the opening and the closing rates and that a single turnover event often involves multiple rounds of conformational switching. In this work, we showed that the repeated conformational transitions of adenylate kinase are essential for the relaxation of incorrectly bound substrates into the catalytically competent conformation by combining all-atom and coarse-grained molecular simulations. In addition, free energy calculations based on all-atom and coarse-grained models demonstrated that the enzyme with incorrectly bound substrates has much a lower free energy barrier for domain opening compared to that with the correct substrate conformation, which may explain the the acceleration of the domain opening rate by substrate binding. The results of this work provide mechanistic understanding to previous experimental observations and shed light onto the interplay between conformational dynamics and enzyme catalysis.

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Section: Introductionmentioning

confidence: 99%

Role of Repeated Conformational Transitions in Substrate Binding of Adenylate Kinase

Scheerer

Haran

et al. 2022

J. Phys. Chem. B

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“…In this study, the proposed MIP procedure involved construction of PCIs and recognition sites by adding templates in the special solvent systems of fabricated hinge-mediated MIPs on a QCM chip. Orädd et al [ 42 ] also showed the closing and opening conformational transitions that characterize conformational dynamics during AK catalysis using time-resolved X-ray solution scattering (TR-XSS). Their results demonstrated that the conformational selection in the domain closure could be considered an induced-fit mechanism.…”

Section: Resultsmentioning

confidence: 99%

Integration of Adenylate Kinase 1 with Its Peptide Conformational Imprint

Lin

et al. 2022

IJMS

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In the present study, molecularly imprinted polymers (MIPs) were used as a tool to grasp a targeted α-helix or β-sheet of protein. During the fabrication of the hinge-mediated MIPs, elegant cavities took shape in a special solvent on quartz crystal microbalance (QCM) chips. The cavities, which were complementary to the protein secondary structure, acted as a peptide conformational imprint (PCI) for adenylate kinase 1 (AK1). We established a promising strategy to examine the binding affinities of human AK1 in conformational dynamics using the peptide-imprinting method. Moreover, when bound to AK1, PCIs are able to gain stability and tend to maintain higher catalytic activities than free AK1. Such designed fixations not only act on hinges as accelerators; some are also inhibitors. One example of PCI inhibition of AK1 catalytic activity takes place when PCI integrates with an AK19-23 β-sheet. In addition, conformation ties, a general MIP method derived from random-coil AK1133-144 in buffer/acetonitrile, are also inhibitors. The inhibition may be due to the need for this peptide to execute conformational transition during catalysis.

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“…On the other hand, most enzymes do not exhibit such behav-ior, although both motor proteins and enzymes catalyze chemical reactions. In particular, enzymes exhibit a distinctive type of dynamics, i.e., conformational change, generally induced by substrate binding and product release [6,7]. Then, it follows that enzymes undergo a conformational change in each turnover cycle of the chemical reactions in the presence of substrate molecules, as shown in Fig.…”

Section: Conformational Dynamics During Chemical Reactionsmentioning

confidence: 99%

“…For the active case, however, the disturbance flow is induced even in a quiescent fluid because of the mechanical work driven by motor proteins or enzymatic molecules. Over the length scale of molecular proteins where the inertial effect is negligible, the hydrodynamic behavior is governed by the well-known Stokes equation η∇ 2 v(r) − ∇p(r) + F(r) = 0, (7) and the incompressibility condition…”

Section: A Continuum Hydrodynamic Descriptionmentioning

confidence: 99%

Nonequilibrium Transport Induced by Biological Nanomachines

Hosaka¹,

Komura²

2022

Preprint

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Biological nanomachines are nanometer-size macromolecular complexes that catalyze chemical reactions in the presence of substrate molecules. The catalytic functions carried out by such nanomachines in the cytoplasm, and biological membranes are essential for cellular metabolism and homeostasis. During catalytic reactions, enzymes undergo conformational changes induced by substrate binding and product release. In recent years, these conformational dynamics have been considered to account for the nonequilibrium transport phenomena such as diffusion enhancement, chemotaxis, and substantial change in rheological properties, which are observed in biological systems. In this review article, we shall give an overview of the recent theoretical and experimental investigations that deal with nonequilibrium transport phenomena induced by biological nanomachines such as enzymes or proteins.

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Tracking the ATP-binding response in adenylate kinase in real time

Abstract: Time-resolved x-ray solution scattering identifies cooperative structural dynamics in the adenylate kinase enzymatic reaction.

Cited by 26 publications

References 88 publications

Role of Repeated Conformational Transitions in Substrate Binding of Adenylate Kinase

Role of Repeated Conformational Transitions in Substrate Binding of Adenylate Kinase

Integration of Adenylate Kinase 1 with Its Peptide Conformational Imprint

Nonequilibrium Transport Induced by Biological Nanomachines

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