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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). 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.

SUBMITTER: Ciupka D

PROVIDER: S-EPMC5556012 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Ciupka Daniel D Gohlke Holger H

Scientific reports 20170814 1

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, conf ...[more]

PMID: 28808308

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