@article{MTMT:2785761,
	title = {Structural and energetic basis of isopropylmalate dehydrogenase enzyme catalysis},
	url = {https://m2.mtmt.hu/api/publication/2785761},
	author = {Palló, A and Oláh, Julianna and Gráczer, Éva Laura and Merli, A and Závodszky, Péter and Weiss, MS and Kazinczyné Vas, Mária},
	doi = {10.1111/febs.13044},
	journal-iso = {FEBS J},
	journal = {FEBS JOURNAL},
	volume = {281},
	unique-id = {2785761},
	issn = {1742-464X},
	abstract = {The three-dimensional structure of the enzyme 3-isopropylmalate dehydrogenase from the bacterium Thermus thermophilus in complex with Mn2+, its substrate isopropylmalate and its co-factor product NADH at 2.0 Å resolution features a fully closed conformation of the enzyme. Upon closure of the two domains, the substrate and the co-factor are brought into precise relative orientation and close proximity, with a distance between the C2 atom of the substrate and the C4N atom of the pyridine ring of the co-factor of approximately 3.0 Å. The structure further shows binding of a K+ ion close to the active site, and provides an explanation for its known activating effect. Hence, this structure is an excellent mimic for the enzymatically competent complex. Using high-level QM/MM calculations, it may be demonstrated that, in the observed arrangement of the reactants, transfer of a hydride from the C2 atom of 3-isopropylmalate to the C4N atom of the pyridine ring of NAD+ is easily possible, with an activation energy of approximately 15 kcal·mol-1. The activation energy increases by approximately 4-6 kcal·mol-1 when the K+ ion is omitted from the calculations. In the most plausible scenario, prior to hydride transfer the ε-amino group of Lys185 acts as a general base in the reaction, aiding the deprotonation reaction of 3-isopropylmalate prior to hydride transfer by employing a low-barrier proton shuttle mechanism involving a water molecule.},
	keywords = {ARTICLE; CATALYSIS; PYRIDINE; nonhuman; Manganese; calculation; X-RAY CRYSTALLOGRAPHY; carboxy terminal sequence; enzyme structure; reduced nicotinamide adenine dinucleotide; potassium ion; enzyme conformation; enzyme active site; enzyme binding; Thermus thermophilus; 3 isopropylmalate dehydrogenase; ISOPROPYLMALATE DEHYDROGENASE; Oxidative decarboxylation; QM/MM calculations; general base catalysis},
	year = {2014},
	eissn = {1742-4658},
	pages = {5063-5076}
}

@article{MTMT:2339846,
	title = {Transient kinetic studies reveal isomerization steps along the kinetic pathway of Thermusthermophilus 3-isopropylmalate dehydrogenase},
	url = {https://m2.mtmt.hu/api/publication/2339846},
	author = {Gráczer, Éva Laura and Lionne, Corinne and Závodszky, Péter and Chaloin, Laurent and Kazinczyné Vas, Mária},
	doi = {10.1111/febs.12191},
	journal-iso = {FEBS J},
	journal = {FEBS JOURNAL},
	volume = {280},
	unique-id = {2339846},
	issn = {1742-464X},
	year = {2013},
	eissn = {1742-4658},
	pages = {1764-1772}
}