Mechanism of methanol oxidation by quinoprotein methanol dehydrogenase

Zhang, Xiaodong; Reddy, Swarnalatha Y.; Bruice, Thomas C.

doi:10.1073/pnas.0610126104

Cited by 31 publications

(18 citation statements)

References 33 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…47,48 This reaction is a formal hydride transfer from the substrate to the metal-ligated C5 carbonyl of the PQQ cofactor, facilitated by the Lewis acidity of the metal ion. 49,50 Single electrons are then transferred from the reduced PQQ cofactor to a c -type cytochrome (XoxG 43,51,52 in the case of Ln-MDH). A Ca- and PQQ-dependent MDH (Ca-MDH, MxaFI) had been known for decades, 53 but the function of XoxF had been cryptic.…”

Section: Lanthanoenzymesmentioning

confidence: 99%

The Chemistry of Lanthanides in Biology: Recent Discoveries, Emerging Principles, and Technological Applications

2019

View full text Add to dashboard Cite

The essential biological role of rare earth elements lay hidden until the discovery in 2011 that lanthanides are specifically incorporated into a bacterial methanol dehydrogenase. Only recently has this observation gone from a curiosity to a major research area, with the appreciation for the widespread nature of lanthanide-utilizing organisms in the environment and the discovery of other lanthanide-binding proteins and systems for selective uptake. While seemingly exotic at first glance, biological utilization of lanthanides is very logical from a chemical perspective. The early lanthanides (La, Ce, Pr, Nd) primarily used by biology are abundant in the environment, perform similar chemistry to other biologically useful metals and do so more efficiently due to higher Lewis acidity, and possess sufficiently distinct coordination chemistry to allow for selective uptake, trafficking, and incorporation into enzymes. Indeed, recent advances in the field illustrate clear analogies with the biological coordination chemistry of other metals, particularly CaII and FeIII, but with unique twists—including cooperative metal binding to magnify the effects of small ionic radius differences—enabling selectivity. This Outlook summarizes the recent developments in this young but rapidly expanding field and looks forward to potential future discoveries, emphasizing continuity with principles of bioinorganic chemistry established by studies of other metals. We also highlight how a more thorough understanding of the central chemical question—selective lanthanide recognition in biology—may impact the challenging problems of sensing, capture, recycling, and separations of rare earths.

show abstract

Section: Lanthanoenzymesmentioning

confidence: 99%

The Chemistry of Lanthanides in Biology: Recent Discoveries, Emerging Principles, and Technological Applications

2019

View full text Add to dashboard Cite

show abstract

“…2F). Based on these studies, pMMO, MDH and MADH appeared to be the most persistent and most important methylotrophy modules, and these became the hallmark enzymes of methylotrophy, demanding much attention and experimental effort in the field (Hakemian and Rosenzweig, 2007; Zhang et al ., 2007; Balasubramanian et al ., 2010; Jensen et al ., 2010; Meschi et al ., 2010). However, emergence of novel types of methylotrophs and the genomic knowledge, combined in some cases with expression and biochemical data, now demonstrate that other combinations of methylotrophy modules are not only possible but may prevail in environmentally significant methylotrophs.…”

Section: How ‘The Parts’ Fit Together (Module Integration)mentioning

confidence: 99%

Modularity of methylotrophy, revisited

Chistoserdova

2011

Environmental Microbiology

342

441

View full text Add to dashboard Cite

SummaryMethylotrophy is a metabolic capability possessed by microorganisms that allows them to build biomass and to obtain energy from organic substrates containing no carbon-carbon bonds (C1 compounds, such as methane, methanol, etc.). This phenomenon in microbial physiology has been a subject of study for over 100 years, elucidating a set of well-defined enzymatic systems and pathways enabling this capability. The knowledge gained from the early genetic and genomic approaches to understanding methylotrophy pointed towards the existence of alternative enzymes/pathways for the specific metabolic goals. Different combinations of these systems in different organisms suggested that methylotrophy must be modular in its nature. More recent insights from genomic analyses, including the genomes representing novel types of methylotrophs, seem to reinforce this notion. This review integrates the new findings with the previously developed concept of modularity of methylotrophy.

show abstract

“…The PES is generated by the adiabatic mapping approach,48,49 incrementally stepping along the P–O bonds and optimizing the geometry of the system at each point with these two distances held fixed. This approach does not extensively sample different conformations of the surrounding enzyme and solvent, so that potential energies are calculated rather than free energies.…”

Section: Introductionmentioning

confidence: 99%

Quantum mechanics/molecular mechanics investigation of the mechanism of phosphate transfer in human uridine-cytidine kinase 2

2009

View full text Add to dashboard Cite

The mechanisms of enzyme-catalyzed phosphate transfer and hydrolysis reactions are of great interest due to their importance and abundance in biochemistry. The reaction may proceed in a stepwise fashion, with either a pentavalent phosphorane or a metaphosphate anion intermediate, or by a concerted S N 2 mechanism. Despite much theoretical work focused on a few key enzymes, a consensus for the mechanism has not been reached, and examples of all three possibilities have been demonstrated. We have investigated the mechanism of human uridine-cytidine kinase 2 (UCK2, EC 2.7.1.48), which catalyzes the transfer of a phosphate group from ATP to the ribose 5′-hydroxyl of cytidine and uridine. UCK2 is normally expressed in human placenta, but is overexpressed in certain cancer cells, where it is responsible for activating a class of antitumor prodrugs. The UCK2 mechanism was investigated by generating a 2D potential energy surface as a function of the P-O bonds forming and breaking, with energies calculated using a quantum mechanics/molecular mechanics potential (B3LYP/6-31G(d):AMBER). The mechanism of phosphate transfer is shown to be concerted, and is accompanied by concerted proton transfer from the 5′-hydroxyl to a conserved active site aspartic acid that serves as a catalytic base. The calculated barrier for this reaction is 15.1 kcal/mol, in relatively good agreement with the experimental barrier of 17.5 kcal/mol. The interactions of the enzyme active site with the reactant, transition state, and product are examined for their implications on the design of anticancer prodrugs or positron emission tomography (PET) reporter probes for this enzyme.

show abstract

Mechanism of methanol oxidation by quinoprotein methanol dehydrogenase

Cited by 31 publications

References 33 publications

The Chemistry of Lanthanides in Biology: Recent Discoveries, Emerging Principles, and Technological Applications

The Chemistry of Lanthanides in Biology: Recent Discoveries, Emerging Principles, and Technological Applications

Modularity of methylotrophy, revisited

Quantum mechanics/molecular mechanics investigation of the mechanism of phosphate transfer in human uridine-cytidine kinase 2

Contact Info

Product

Resources

About