On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase

Abstract The pyruvate phosphate dikinase (PPDK) reaction mechanism is characterized by a distinct spatial separation of reaction centers and large conformational changes involving an opening-closing motion of the nucleotide-binding domain (NBD) and a swiveling motion of the central domain (CD). Howe...

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Autores principales:	Daniel Ciupka, Holger Gohlke
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5148c7bfd75e4a51860c3bbe2fa28754
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spelling	oai:doaj.org-article:5148c7bfd75e4a51860c3bbe2fa287542021-12-02T16:06:52ZOn the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase10.1038/s41598-017-08521-w2045-2322https://doaj.org/article/5148c7bfd75e4a51860c3bbe2fa287542017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08521-whttps://doaj.org/toc/2045-2322Abstract The pyruvate phosphate dikinase (PPDK) reaction mechanism is characterized by a distinct spatial separation of reaction centers and large conformational changes involving an opening-closing motion of the nucleotide-binding domain (NBD) and a swiveling motion of the central domain (CD). However, why PPDK is active only in a dimeric form and to what extent an alternate binding change mechanism could underlie this fact has remained elusive. We performed unbiased molecular dynamics simulations, configurational free energy computations, and rigidity analysis to address this question. Our results support the hypothesis that PPDK dimerization influences the opening-closing motion of the NBDs, and that this influence is mediated via the CDs of both chains. Such an influence would be a prerequisite for an alternate binding change mechanism to occur. To the best of our knowledge, this is the first time that a possible explanation has been suggested as to why only dimeric PPDK is active.Daniel CiupkaHolger GohlkeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel Ciupka Holger Gohlke On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase
description	Abstract The pyruvate phosphate dikinase (PPDK) reaction mechanism is characterized by a distinct spatial separation of reaction centers and large conformational changes involving an opening-closing motion of the nucleotide-binding domain (NBD) and a swiveling motion of the central domain (CD). However, why PPDK is active only in a dimeric form and to what extent an alternate binding change mechanism could underlie this fact has remained elusive. We performed unbiased molecular dynamics simulations, configurational free energy computations, and rigidity analysis to address this question. Our results support the hypothesis that PPDK dimerization influences the opening-closing motion of the NBDs, and that this influence is mediated via the CDs of both chains. Such an influence would be a prerequisite for an alternate binding change mechanism to occur. To the best of our knowledge, this is the first time that a possible explanation has been suggested as to why only dimeric PPDK is active.
format	article
author	Daniel Ciupka Holger Gohlke
author_facet	Daniel Ciupka Holger Gohlke
author_sort	Daniel Ciupka
title	On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase
title_short	On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase
title_full	On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase
title_fullStr	On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase
title_full_unstemmed	On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase
title_sort	on the potential alternate binding change mechanism in a dimeric structure of pyruvate phosphate dikinase
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5148c7bfd75e4a51860c3bbe2fa28754
work_keys_str_mv	AT danielciupka onthepotentialalternatebindingchangemechanisminadimericstructureofpyruvatephosphatedikinase AT holgergohlke onthepotentialalternatebindingchangemechanisminadimericstructureofpyruvatephosphatedikinase
_version_	1718384840414330880

On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase

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