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

This title appears in the Scientific Report : 2017

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

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...

Personal Name(s):	Ciupka, Daniel
	Gohlke, Holger (Corresponding author)
Contributing Institute:	Jülich Supercomputing Center; JSC Strukturbiochemie; ICS-6 John von Neumann - Institut für Computing; NIC
Published in:	Scientific reports, 7 (2017) 1, S. 8020
Imprint:	London Nature Publishing Group 2017
DOI:	10.1038/s41598-017-08521-w
Document Type:	Journal Article
Research Program:	Physical Basis of Diseases Investigating the swiveling domain mechanism of the Pyruvate phosphate dikinase (PPDK) Computational Science and Mathematical Methods
Link:	OpenAccess OpenAccess
	Publikationsportal JuSER

Please use the identifier: http://dx.doi.org/10.1038/s41598-017-08521-w in citations.
Please use the identifier: http://hdl.handle.net/2128/15158 in citations.

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.