Journal of Chemical Information and Modeling, volume 57, issue 8, pages 1999-2008
Role of Protein Dimeric Interface in Allosteric Inhibition of N-Acetyl-Aspartate Hydrolysis by Human Aspartoacylase
Publication type: Journal Article
Publication date: 2017-08-04
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 5.6
ISSN: 15499596, 1549960X
General Chemistry
Computer Science Applications
General Chemical Engineering
Library and Information Sciences
Abstract
The results of molecular modeling suggest a mechanism of allosteric inhibition upon hydrolysis of N-acetyl-aspartate (NAA), one of the most abundant amino acid derivatives in brain, by human aspartoacylase (hAsp). Details of this reaction are important to suggest the practical ways to control the enzyme activity. Search for allosteric sites using the Allosite web server and SiteMap analysis allowed us to identify substrate binding pockets located at the interface between the subunits of the hAsp dimer molecule. Molecular docking of NAA to the pointed areas at the dimer interface predicted a specific site, in which the substrate molecule interacts with the Gly237, Arg233, Glu290, and Lys292 residues. Analysis of multiple long-scaled molecular dynamics trajectories (the total simulation time exceeded 1.5 μs) showed that binding of NAA to the identified allosteric site induced significant rigidity to the protein loops with the amino acid side chains forming gates to the enzyme active site. Application of the protein dynamical network algorithms showed that substantial reorganization of the signal propagation pathways of intersubunit communication in the dimer occurred upon allosteric NAA binding to the remote site. The modeling approaches provide an explanation to the observed decrease of the reaction rate of NAA hydrolysis by hAsp at high substrate concentrations.
Citations by journals
1
2
|
|
ACS Chemical Neuroscience
|
ACS Chemical Neuroscience
2 publications, 11.11%
|
Biophysics (Russian Federation)
|
Biophysics (Russian Federation)
2 publications, 11.11%
|
Journal of Biomolecular Structure and Dynamics
|
Journal of Biomolecular Structure and Dynamics
2 publications, 11.11%
|
Russian Chemical Bulletin
|
Russian Chemical Bulletin
1 publication, 5.56%
|
Russian Chemical Reviews
|
Russian Chemical Reviews
1 publication, 5.56%
|
Moscow University Chemistry Bulletin
|
Moscow University Chemistry Bulletin
1 publication, 5.56%
|
Journal of Chemical Information and Modeling
|
Journal of Chemical Information and Modeling
1 publication, 5.56%
|
Journal of Physical Chemistry B
|
Journal of Physical Chemistry B
1 publication, 5.56%
|
Frontiers in Molecular Biosciences
|
Frontiers in Molecular Biosciences
1 publication, 5.56%
|
Scientific Reports
|
Scientific Reports
1 publication, 5.56%
|
Journal of Molecular Biology
|
Journal of Molecular Biology
1 publication, 5.56%
|
Chemical Physics Letters
|
Chemical Physics Letters
1 publication, 5.56%
|
Doklady Physical Chemistry
|
Doklady Physical Chemistry
1 publication, 5.56%
|
Doklady Biochemistry and Biophysics
|
Doklady Biochemistry and Biophysics
1 publication, 5.56%
|
Advances in Protein Chemistry and Structural Biology
|
Advances in Protein Chemistry and Structural Biology
1 publication, 5.56%
|
1
2
|
Citations by publishers
1
2
3
4
5
|
|
Pleiades Publishing
|
Pleiades Publishing
5 publications, 27.78%
|
American Chemical Society (ACS)
|
American Chemical Society (ACS)
4 publications, 22.22%
|
Elsevier
|
Elsevier
3 publications, 16.67%
|
Springer Nature
|
Springer Nature
2 publications, 11.11%
|
Taylor & Francis
|
Taylor & Francis
2 publications, 11.11%
|
Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii
|
Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii
1 publication, 5.56%
|
Frontiers Media S.A.
|
Frontiers Media S.A.
1 publication, 5.56%
|
1
2
3
4
5
|
- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
{"yearsCitations":{"type":"bar","data":{"show":true,"labels":[2017,2018,2019,2020,2021,2022],"ids":[0,0,0,0,0,0],"codes":[0,0,0,0,0,0],"imageUrls":["","","","","",""],"datasets":[{"label":"Citations number","data":[1,4,6,4,1,2],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":["5.56","22.22","33.33","22.22","5.56","11.11"],"barThickness":null}]},"options":{"indexAxis":"x","maintainAspectRatio":true,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":1,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Citations per year","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"journals":{"type":"bar","data":{"show":true,"labels":["ACS Chemical Neuroscience","Biophysics (Russian Federation)","Journal of Biomolecular Structure and Dynamics","Russian Chemical Bulletin","Russian Chemical Reviews","Moscow University Chemistry Bulletin","Journal of Chemical Information and Modeling","Journal of Physical Chemistry B","Frontiers in Molecular Biosciences","Scientific Reports","Journal of Molecular Biology","Chemical Physics Letters","Doklady Physical Chemistry","Doklady Biochemistry and Biophysics","Advances in Protein Chemistry and Structural Biology"],"ids":[5507,24903,3040,10918,23802,10010,13608,14990,3133,13767,19701,5579,12181,3773,2738],"codes":[0,0,0,0,0,0,0,0,0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/oZgeErrVFhuDksyqFURLvYS1wtVSBWczh001igGo_medium.webp","\/storage\/images\/resized\/5YZtvLvkPZuc2JHOaZsjCvGSHFCuC3drUwN3YAc5_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/9Mus3KG1Tkd7Bwaurt8H3RwWh0CxRlGoO6ng9UK1_medium.webp","\/storage\/images\/resized\/oZgeErrVFhuDksyqFURLvYS1wtVSBWczh001igGo_medium.webp","\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/oZgeErrVFhuDksyqFURLvYS1wtVSBWczh001igGo_medium.webp","\/storage\/images\/resized\/oZgeErrVFhuDksyqFURLvYS1wtVSBWczh001igGo_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp"],"datasets":[{"label":"","data":[2,2,2,1,1,1,1,1,1,1,1,1,1,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[11.11,11.11,11.11,5.56,5.56,5.56,5.56,5.56,5.56,5.56,5.56,5.56,5.56,5.56,5.56],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Journals","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"publishers":{"type":"bar","data":{"show":true,"labels":["Pleiades Publishing","American Chemical Society (ACS)","Elsevier","Springer Nature","Taylor & Francis","Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii","Frontiers Media S.A."],"ids":[101,40,17,8,18,9422,208],"codes":[0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/oZgeErrVFhuDksyqFURLvYS1wtVSBWczh001igGo_medium.webp","\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/5YZtvLvkPZuc2JHOaZsjCvGSHFCuC3drUwN3YAc5_medium.webp","\/storage\/images\/resized\/9Mus3KG1Tkd7Bwaurt8H3RwWh0CxRlGoO6ng9UK1_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp"],"datasets":[{"label":"","data":[5,4,3,2,2,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[27.78,22.22,16.67,11.11,11.11,5.56,5.56],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Publishers","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}}}
Metrics
Cite this
GOST |
RIS |
BibTex |
MLA
Cite this
GOST
Copy
Kots E. et al. Role of Protein Dimeric Interface in Allosteric Inhibition of N-Acetyl-Aspartate Hydrolysis by Human Aspartoacylase // Journal of Chemical Information and Modeling. 2017. Vol. 57. No. 8. pp. 1999-2008.
GOST all authors (up to 50)
Copy
Kots E., Lushchekina S., Varfolomeev S. D., Nemukhin A. Role of Protein Dimeric Interface in Allosteric Inhibition of N-Acetyl-Aspartate Hydrolysis by Human Aspartoacylase // Journal of Chemical Information and Modeling. 2017. Vol. 57. No. 8. pp. 1999-2008.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1021/acs.jcim.7b00133
UR - https://doi.org/10.1021%2Facs.jcim.7b00133
TI - Role of Protein Dimeric Interface in Allosteric Inhibition of N-Acetyl-Aspartate Hydrolysis by Human Aspartoacylase
T2 - Journal of Chemical Information and Modeling
AU - Kots, Ekaterina D.
AU - Nemukhin, Alexander
AU - Lushchekina, S.
AU - Varfolomeev, S. D.
PY - 2017
DA - 2017/08/04 00:00:00
PB - American Chemical Society (ACS)
SP - 1999-2008
IS - 8
VL - 57
SN - 1549-9596
SN - 1549-960X
ER -
Cite this
BibTex
Copy
@article{2017_Kots,
author = {Ekaterina D. Kots and Alexander Nemukhin and S. Lushchekina and S. D. Varfolomeev},
title = {Role of Protein Dimeric Interface in Allosteric Inhibition of N-Acetyl-Aspartate Hydrolysis by Human Aspartoacylase},
journal = {Journal of Chemical Information and Modeling},
year = {2017},
volume = {57},
publisher = {American Chemical Society (ACS)},
month = {aug},
url = {https://doi.org/10.1021%2Facs.jcim.7b00133},
number = {8},
pages = {1999--2008},
doi = {10.1021/acs.jcim.7b00133}
}
Cite this
MLA
Copy
Kots, Ekaterina D., et al. “Role of Protein Dimeric Interface in Allosteric Inhibition of N-Acetyl-Aspartate Hydrolysis by Human Aspartoacylase.” Journal of Chemical Information and Modeling, vol. 57, no. 8, Aug. 2017, pp. 1999-2008. https://doi.org/10.1021%2Facs.jcim.7b00133.
Profiles