Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.

The relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].

Please format your output as a JSON array. Each entry in the array should express a single relation, formatted as ["<Entity_A>", "<RELATION_A_B>", "<Entity_B>"]. If no relations can be found, please output an empty JSON array [].

Abstract:

Fast protein motions are coupled to enzyme H-transfer reactions. Coupling of fast protein dynamics to enzyme chemistry is controversial and has ignited considerable debate, especially over the past 15 years in relation to enzyme-catalyzed H-transfer. H-transfer can occur by quantum tunneling, and the temperature dependence of kinetic isotope effects (KIEs) has emerged as the " gold standard " descriptor of these reactions. The anomalous temperature dependence of KIEs is often rationalized by invoking fast motions to facilitate H-transfer, yet crucially, direct evidence for coupled motions is lacking. The fast motions hypothesis underpinning the temperature dependence of KIEs is based on inference. Here, we have perturbed vibrational motions in pentaerythritol tetranitrate reductase (PETNR) by isotopic substitution where all non-exchangeable atoms were replaced with the corresponding heavy isotope ((13) C, (15) N, and (2) H). The KIE temperature dependence is perturbed by heavy isotope labeling, demonstrating a direct link between (promoting) vibrations in the protein and the observed KIE. Further we show that temperature-independent KIEs do not necessarily rule out a role for fast dynamics coupled to reaction chemistry. We show causality between fast motions and enzyme chemistry and demonstrate how this impacts on experimental KIEs for enzyme reactions.
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