Reflections on the catalytic power of a TIM-barrel

Richard, John P.; Zhai, Xiang; Malabanan, M. Merced

doi:10.1016/j.bioorg.2014.07.001

Cited by 37 publications

(79 citation statements)

References 80 publications

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“…Interestingly, from both these studies, the most promising folds generated in silico that had high catalytic efficiencies were triose‐phosphate‐isomerase (TIM) type containing eight alpha and beta helices. TIM toroids are known to be very effective for enzymatic reactions, and thus this shows convergence between in vivo and in silico fold preference.…”

Section: Successesmentioning

confidence: 99%

From directed evolution to computational enzyme engineering—A review

Chowdhury

Maranas

2019

AIChE Journal

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Nature relies on a wide range of enzymes with specific biocatalytic roles to carry out much of the chemistry needed to sustain life. Enzymes catalyze the interconversion of a vast array of molecules with high specificity-from molecular nitrogen fixation to the synthesis of highly specialized hormones and quorum-sensing molecules. Ever increasing emphasis on renewable sources for energy and waste minimization has turned enzymes into key industrial workhorses for targeted chemical conversions. Modern enzymology is central to not only food and beverage manufacturing processes but also finds relevance in countless consumer product formulations such as proteolytic enzymes in detergents, amylases for excess bleach removal from textiles, proteases in meat tenderization, and lactoperoxidases in dairy products. Herein, we present an overview of enzyme science and engineering milestones and the emergence of directed evolution of enzymes for which the 2018 Nobel Prize in Chemistry was awarded to Dr. Frances Arnold. K E Y W O R D Sbiocatalysis, computational protein design, directed evolution, enzyme engineering, mutagenesis

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Section: Successesmentioning

confidence: 99%

From directed evolution to computational enzyme engineering—A review

Chowdhury

Maranas

2019

AIChE Journal

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“…The barrier for conversion of E O to E C represents, minimally, the barriers to extrusion of protein bound waters to bulk solvent, and to freezing of large conformational motions of the flexible protein loops and of catalytic side chains at the ordered structure for the active protein-substrate cage. 3, 8, 42, 44, 45 …”

Section: Transition State Stabilization From Protein-dianion Bindingmentioning

confidence: 99%

A reevaluation of the origin of the rate acceleration for enzyme-catalyzed hydride transfer

2017

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There is no consensus of opinion on the origin of the large rate accelerations observed for enzyme-catalyzed hydride transfer. The interpretation of recent results from studies on hydride transfer reactions catalyzed by alcohol dehydrogenase (ADH) focus on the proposal that the effective barrier height is reduced by quantum-mechanical tunneling through the energy barrier. This interpretation contrasts sharply with the notion that enzymatic rate accelerations are obtained through direct stabilization of the transition state for the nonenzymatic reaction in water. The binding energy of the dianion of substrate for DHAP provides 11 kcal/mol stabilization of the transition state for the hydride transfer reaction catalyzed by glycerol-3-phosphate dehydrogenase (GPDH). We summarize evidence that the binding interactions between (GPDH) and dianion activators are utilized directly for stabilization of the transition state for enzyme-catalyzed hydride transfer. The possibility is considered, and then discounted, that these dianion binding interactions are utilized for the stabilization of a tunnel ready state (TRS) that enables efficient tunneling of the transferred hydride through the energy barrier, and underneath the energy maximum for the transition state. It is noted that the evidence to support the existence of a tunnel-ready state for the hydride transfer reactions catalyzed by ADH is ambiguous. We propose that the rate acceleration for ADH is due to the utilization of the binding energy of the cofactor in the stabilization of the transition state for enzyme-catalyzed hydride transfer.

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“…It is likely that its meandering topology and consolidated b-barrel aid its folding, stabilization and functionalization. In turn, this may help explain the predominance of the TIM barrel in nature, where it accounts for 10% of all of the known enzyme structures [20,21]. In these respects of folding kinetics and adaptability for function, it may be a privileged fold, or at least one very good solution to the protein folding/function problem.…”

Section: Introduction and Scope Of This Reviewmentioning

confidence: 95%

De novo protein design: how do we expand into the universe of possible protein structures?

Woolfson

Bartlett

Burton

et al. 2015

Current Opinion in Structural Biology

157

161

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Protein scientists are paving the way to a new phase in protein design and engineering. Approaches and methods are being developed that could allow the design of proteins beyond the confines of natural protein structures. This possibility of designing entirely new proteins opens new questions: What do we build? How do we build into protein-structure space where there are few, if any, natural structures to guide us? To what uses can the resulting proteins be put? And, what, if anything, does this pursuit tell us about how natural proteins fold, function and evolve? We describe the origins of this emerging area of fully de novo protein design, how it could be developed, where it might lead, and what challenges lie ahead.

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Reflections on the catalytic power of a TIM-barrel

Cited by 37 publications

References 80 publications

From directed evolution to computational enzyme engineering—A review

From directed evolution to computational enzyme engineering—A review

A reevaluation of the origin of the rate acceleration for enzyme-catalyzed hydride transfer

De novo protein design: how do we expand into the universe of possible protein structures?

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