TY  - JOUR
AU  - Palló, A
AU  - Oláh, Julianna
AU  - Gráczer, Éva Laura
AU  - Merli, A
AU  - Závodszky, Péter
AU  - Weiss, MS
AU  - Kazinczyné Vas, Mária
TI  - Structural and energetic basis of isopropylmalate dehydrogenase enzyme catalysis
JF  - FEBS JOURNAL
J2  - FEBS J
VL  - 281
PY  - 2014
IS  - 22
SP  - 5063
EP  - 5076
PG  - 14
SN  - 1742-464X
DO  - 10.1111/febs.13044
UR  - https://m2.mtmt.hu/api/publication/2785761
ID  - 2785761
N1  - Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary            
            Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Budapest, Hungary            
            Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, Budapest, H-1117, Hungary            
            Dipartimento di Bioscienze, Universitá Degli Studi di Parma, Parma, Italy            
            Helmholtz Zentrum Berlin für Materialien und Energie, Macromolecular Crystallography, Albert Einstein Straße 15, Berlin, D-12489, Germany            
            Structural Biology Research Center, Vlaams Instituut voor Biotechnologie, Brussels, B-1050, Belgium            
            Brussels Center for Redox Biology, Brussels, B-1050, Belgium            
            Structural Biology Brussels Laboratory, Vrije Universiteit Brussel, Brussels, B-1050, Belgium            
            Cited By :12            
            Export Date: 15 April 2021            
            CODEN: FJEOA            
            Correspondence Address: Weiss, M.S.; Helmholtz Zentrum Berlin für Materialien und Energie, Albert Einstein Straße 15, Germany; email: manfred.weiss@helmholtz-berlin.de            
            Chemicals/CAS: 3 isopropylmalate dehydrogenase, 9030-97-1; magnesium, 7439-95-4; manganese, 16397-91-4, 7439-96-5; nicotinamide adenine dinucleotide, 53-84-9; potassium, 7440-09-7; 3-Isopropylmalate Dehydrogenase; Bacterial Proteins; Magnesium; Malates; Manganese; NAD; Potassium            
            Funding details: Hungarian Scientific Research Fund, OTKA, 108642
AB  - 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.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Gráczer, Éva Laura
AU  - Lionne, Corinne
AU  - Závodszky, Péter
AU  - Chaloin, Laurent
AU  - Kazinczyné Vas, Mária
TI  - Transient kinetic studies reveal isomerization steps along the kinetic pathway of Thermusthermophilus 3-isopropylmalate dehydrogenase
JF  - FEBS JOURNAL
J2  - FEBS J
VL  - 280
PY  - 2013
IS  - 8
SP  - 1764
EP  - 1772
PG  - 9
SN  - 1742-464X
DO  - 10.1111/febs.12191
UR  - https://m2.mtmt.hu/api/publication/2339846
ID  - 2339846
N1  - Megjegyzés-23169602
N1 : Chemicals/CAS3 isopropylmalate dehydrogenase, 9030-97-1; magnesium ion, 22537-22-0; reduced nicotinamide adenine dinucleotide, 58-68-4; tryptophan, 6912-86-3, 73-22-3
Megjegyzés-23169791
N1 : Chemicals/CAS3 isopropylmalate dehydrogenase, 9030-97-1; magnesium ion, 22537-22-0; reduced nicotinamide adenine dinucleotide, 58-68-4; tryptophan, 6912-86-3, 73-22-3
Megjegyzés-23174472
N1 : Chemicals/CAS3 isopropylmalate dehydrogenase, 9030-97-1; magnesium ion, 22537-22-0; reduced nicotinamide adenine dinucleotide, 58-68-4; tryptophan, 6912-86-3, 73-22-3
LA  - English
DB  - MTMT
ER  -