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Title: Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase

Abstract

Crystal structures of adenylate kinase (AdK) from Escherichia coli capture two states: an “open” conformation (apo) obtained in the absence of ligands and a “closed” conformation in which ligands are bound. Other AdK crystal structures suggest intermediate conformations that may lie on the transition pathway between these two states. To characterize the transition from open to closed states in solution, X-ray solution scattering data were collected from AdK in the apo form and with progressively increasing concentrations of five different ligands. Scattering data from apo AdK are consistent with scattering predicted from the crystal structure of AdK in the open conformation. In contrast, data from AdK samples saturated with Ap5A do not agree with that calculated from AdK in the closed conformation. Using cluster analysis of available structures, we selected representative structures in five conformational states: open, partially open, intermediate, partially closed, and closed. We used these structures to estimate the relative abundances of these states for each experimental condition. X-ray solution scattering data obtained from AdK with AMP are dominated by scattering from AdK in the open conformation. For AdK in the presence of high concentrations of ATP and ADP, the conformational ensemble shifts to a mixture of partiallymore » open and closed states. Even when AdK is saturated with Ap5A, a significant proportion of AdK remains in a partially open conformation. Here, these results are consistent with an induced-fit model in which the transition of AdK from an open state to a closed state is initiated by ATP binding.« less

Authors:
 [1];  [2];  [3];  [3];  [3];  [4];  [3];  [3]; ORCiD logo [5]; ORCiD logo [3]
  1. Univ. of California, Los Angeles, CA (United States)
  2. DeltaG Technologies, San Diego, CA (United States)
  3. Northeastern Univ., Boston, MA (United States)
  4. Univ. of Pittsburgh, Pittsburgh, PA (United States)
  5. Illinois Inst. of Technology, Chicago, IL (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Science Foundation (NSF); National Inst. of Health
OSTI Identifier:
1432856
Grant/Contract Number:  
MCB-1158340; R01-GM85648
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Biochemistry
Additional Journal Information:
Journal Volume: 56; Journal Issue: 34; Journal ID: ISSN 0006-2960
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; ligands; crystal structure; scattering; conformation; cluster chemistry; induced fit; conformational transition; ligand binding; SAXS; adneylate kinase; structural ensembles

Citation Formats

Onuk, Emre, Badger, John, Wang, Yu Jing, Bardhan, Jaydeep, Chishti, Yasmin, Akcakaya, Murat, Brooks, Dana H., Erdogmus, Deniz, Minh, David D. L., and Makowski, Lee. Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase. United States: N. p., 2017. Web. doi:10.1021/acs.biochem.7b00351.
Onuk, Emre, Badger, John, Wang, Yu Jing, Bardhan, Jaydeep, Chishti, Yasmin, Akcakaya, Murat, Brooks, Dana H., Erdogmus, Deniz, Minh, David D. L., & Makowski, Lee. Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase. United States. doi:10.1021/acs.biochem.7b00351.
Onuk, Emre, Badger, John, Wang, Yu Jing, Bardhan, Jaydeep, Chishti, Yasmin, Akcakaya, Murat, Brooks, Dana H., Erdogmus, Deniz, Minh, David D. L., and Makowski, Lee. Wed . "Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase". United States. doi:10.1021/acs.biochem.7b00351. https://www.osti.gov/servlets/purl/1432856.
@article{osti_1432856,
title = {Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase},
author = {Onuk, Emre and Badger, John and Wang, Yu Jing and Bardhan, Jaydeep and Chishti, Yasmin and Akcakaya, Murat and Brooks, Dana H. and Erdogmus, Deniz and Minh, David D. L. and Makowski, Lee},
abstractNote = {Crystal structures of adenylate kinase (AdK) from Escherichia coli capture two states: an “open” conformation (apo) obtained in the absence of ligands and a “closed” conformation in which ligands are bound. Other AdK crystal structures suggest intermediate conformations that may lie on the transition pathway between these two states. To characterize the transition from open to closed states in solution, X-ray solution scattering data were collected from AdK in the apo form and with progressively increasing concentrations of five different ligands. Scattering data from apo AdK are consistent with scattering predicted from the crystal structure of AdK in the open conformation. In contrast, data from AdK samples saturated with Ap5A do not agree with that calculated from AdK in the closed conformation. Using cluster analysis of available structures, we selected representative structures in five conformational states: open, partially open, intermediate, partially closed, and closed. We used these structures to estimate the relative abundances of these states for each experimental condition. X-ray solution scattering data obtained from AdK with AMP are dominated by scattering from AdK in the open conformation. For AdK in the presence of high concentrations of ATP and ADP, the conformational ensemble shifts to a mixture of partially open and closed states. Even when AdK is saturated with Ap5A, a significant proportion of AdK remains in a partially open conformation. Here, these results are consistent with an induced-fit model in which the transition of AdK from an open state to a closed state is initiated by ATP binding.},
doi = {10.1021/acs.biochem.7b00351},
journal = {Biochemistry},
issn = {0006-2960},
number = 34,
volume = 56,
place = {United States},
year = {2017},
month = {8}
}

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