NAD+-dependent formate dehydrogenase

Popov, Vladimir O.; Lamzin, Victor S.

doi:10.1042/bj3010625

Cited by 260 publications

(258 citation statements)

References 104 publications

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“…We report a study of the enzyme formate dehydrogenase (FDH) that catalyzes the nicotinamide adenine dinucleotide (NAD þ )-dependent oxidation of formate to carbon dioxide via hydride transfer to the C-4 carbon of the nicotinamide ring of NAD þ (37,38). FDH is an industrially important enzyme in the regeneration of NADH and NADPH for biocatalysis (39,40). Azide, which is an excellent vibrational chromophore, is a tightbinding inhibitor for FDH with an inhibition constant that we have measured as K i ¼ 40 nM.…”

Section: D Ir Spectroscopy | Enzyme Dynamicsmentioning

confidence: 99%

Characterizing the dynamics of functionally relevant complexes of formate dehydrogenase

Bandaria

Dutta

Nydegger

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

118

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The potential for femtosecond to picosecond time-scale motions to influence the rate of the intrinsic chemical step in enzymecatalyzed reactions is a source of significant controversy. Among the central challenges in resolving this controversy is the difficulty of experimentally characterizing thermally activated motions at this time scale in functionally relevant enzyme complexes. We report a series of measurements to address this problem using twodimensional infrared spectroscopy to characterize the time scales of active-site motions in complexes of formate dehydrogenase with the transition-state-analog inhibitor azide (N − 3 ). We observe that the frequency-frequency time correlation functions (FFCF) for the ternary complexes with NAD þ and NADH decay completely with slow time constants of 3.2 ps and 4.6 ps, respectively. This result suggests that in the vicinity of the transition state, the active-site enzyme structure samples a narrow and relatively rigid conformational distribution indicating that the transition-state structure is well organized for the reaction. In contrast, for the binary complex, we observe a significant static contribution to the FFCF similar to what is seen in other enzymes, indicating the presence of the slow motions that occur on time scales longer than our measurement window. 2D IR spectroscopy | enzyme dynamicsT he functional role of protein motions at the femtosecond to picosecond time scale is a hotly debated topic in enzymology. Although such a role could be general in nature, many experimental (1-10) and theoretical (11-23) studies of enzymecatalyzed hydrogen transfers have invoked protein motions at this time scale to explain anomalous kinetic isotope effects (KIE) and their temperature dependence. These studies result in the development of theoretical models, often referred to as Marcus-like models, in which the environmental reorganization that precedes the hydrogen-tunneling event has evolved to optimize the conformation of the transition state for tunneling (1,7,24). Fig. 1 illustrates the physical picture underlying such models. Heavy atom motions along the reorganization coordinate carry the system to a point where the donor and acceptor wells in the double-well hydrogen atom potential are degenerate and tunneling can proceed. At this position, the donor-acceptor distance and its fluctuations determine the tunneling probability. Mathematically, the rate constant for hydrogen transfer in these models is given by expressions of the form where C is the fraction of reactive complexes, the first exponential, in analogy with the Marcus theory for electron transfer, reflects the reorganization of the heavy atoms that modulates the relative energies of the reactants and the products to minimize the energy defect between the zero-point levels of the donor and acceptor wells. ΔG°is the driving force for the reaction, and λ is the reorganization energy. The second exponential gives the overlap between the donor and acceptor wave functions as a function of the donor-acceptor distan...

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Section: D Ir Spectroscopy | Enzyme Dynamicsmentioning

confidence: 99%

Characterizing the dynamics of functionally relevant complexes of formate dehydrogenase

Bandaria

Dutta

Nydegger

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

118

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“…Replacement of glutamate for glutamine is highly specific and conserved throughout all known FDH sequences [11]. The glutamine residue is located within the Pro-Gln-ProAla-Pro fingerprint.…”

Section: Introductionmentioning

confidence: 99%

“…In FDH the two prolines flanking Gln 313 are in the cis-conformation and force the amide group of the glutamine to face His 332 NE2. As a result of this interaction His 332 forms a tight H-bond (2.8 A) with Gln 313 NE2 and is trapped in a non-protonated state [2,10,11].…”

Section: Introductionmentioning

confidence: 99%

Site‐directed mutagenesis of the formate dehydrogenase active centre: role of the His³³²‐Gln³¹³ pair in enzyme catalysis

et al. 1996

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“…1) D-lactate, [2][3][4] D-hydroxyisocaproate, 5) D-glycerate, 6) and D-erythronate-4-phosphate 7) dehydrogenases, vancomycin-resistant protein H (VanH), 8,9) glyoxylate reductase (GR), 10) and transcriptional co-repressor CtBP, 11) share a common protein structure and constitute the D-2-HydDH family, 12) together with some non-D-2-HydDHs, such as the formate, 13) phosphite, 14,15) and L-alanine 16) dehydrogenases. It has been reported that only minor structural changes, such as amino acid replacements, cause drastic change, in the enzyme function in this family, as for example, conversions from a D-lactate dehydrogenase (D-LDH) to a D-hydroxyisocaproate dehydrogenase (D-HicDH), 17,18) and even from a formate dehydrogenase to a D-2-HydDH.…”

mentioning

confidence: 99%

A New Family ofD-2-Hydroxyacid Dehydrogenases That ComprisesD-Mandelate Dehydrogenases and 2-Ketopantoate Reductases

Wada

Iwai

Tamura

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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NAD+-dependent formate dehydrogenase

Cited by 260 publications

References 104 publications

Characterizing the dynamics of functionally relevant complexes of formate dehydrogenase

Characterizing the dynamics of functionally relevant complexes of formate dehydrogenase

Site‐directed mutagenesis of the formate dehydrogenase active centre: role of the His³³²‐Gln³¹³ pair in enzyme catalysis

A New Family ofD-2-Hydroxyacid Dehydrogenases That ComprisesD-Mandelate Dehydrogenases and 2-Ketopantoate Reductases

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NAD+-dependent formate dehydrogenase

Cited by 260 publications

References 104 publications

Characterizing the dynamics of functionally relevant complexes of formate dehydrogenase

Characterizing the dynamics of functionally relevant complexes of formate dehydrogenase

Site‐directed mutagenesis of the formate dehydrogenase active centre: role of the His332‐Gln313 pair in enzyme catalysis

A New Family ofD-2-Hydroxyacid Dehydrogenases That ComprisesD-Mandelate Dehydrogenases and 2-Ketopantoate Reductases

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Site‐directed mutagenesis of the formate dehydrogenase active centre: role of the His³³²‐Gln³¹³ pair in enzyme catalysis