Structural optimization of SadA, an Fe(II)- and α-ketoglutarate-dependent dioxygenase targeting biocatalytic synthesis of N-succinyl-l-threo-3,4-dimethoxyphenylserine

Qin, Hao; Miyakawa, Takuya; Nakamura, Akira; Hibi, Makoto; Ogawa, Jun; Tanokura, Masaru

doi:10.1016/j.bbrc.2014.07.008

Cited by 19 publications

(21 citation statements)

References 18 publications

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“…40) Their importance in the substrate specificity is supported by the result that the F261A mutant exhibits increased activity toward N-succinyl-L-3,4-dimethoxyphenylalanine (NSDOPA), 41) which is converted to N-succinyl-L-threo-3,4-dihydroxyphenylserine, a precursor of L-DOPS, and possesses a bulkier sidechain than NSLeu. The results also show that the structural information is useful for the improvement of substrate specificity, which is a major target of the rational design of useful enzymes based on protein engineering.…”

Section: Stereoselective Catalytic Mechanism Of Dioxygenase and mentioning

confidence: 89%

“…[37][38][39] The SadA structure provides the mechanistic basis for the stereoselective reaction of NSLeu to make the expansion of substrate specificity possible. 40,41) SadA forms a dimeric structure, and each protomer adopts a double-stranded β-helix (DSBH) fold at the core of the structure, along with six α-helices (Fig. 4(A)).…”

Section: Stereoselective Catalytic Mechanism Of Dioxygenase and mentioning

confidence: 99%

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Structural analysis of enzymes used for bioindustry and bioremediation

Tanokura

Miyakawa

Guan

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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Microbial enzymes have been widely applied in the large-scale, bioindustrial manufacture of food products and pharmaceuticals due to their high substrate specificity and stereoselectivity, and their effectiveness under mild conditions with low environmental burden. At the same time, bioremedial techniques using microbial enzymes have been developed to solve the problem of industrial waste, particularly with respect to persistent chemicals and toxic substances. And finally, structural studies of these enzymes have revealed the mechanistic basis of enzymatic reactions, including the stereoselectivity and binding specificity of substrates and cofactors. The obtained structural insights are useful not only to deepen our understanding of enzymes with potential bioindustrial and/or bioremedial application, but also for the functional improvement of enzymes through rational protein engineering. This review shows the structural bases for various types of enzymatic reactions, including the substrate specificity accompanying cofactor-controlled and kinetic mechanisms.

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Section: Stereoselective Catalytic Mechanism Of Dioxygenase and mentioning

confidence: 89%

Section: Stereoselective Catalytic Mechanism Of Dioxygenase and mentioning

confidence: 99%

Structural analysis of enzymes used for bioindustry and bioremediation

Tanokura

Miyakawa

Guan

et al. 2015

Bioscience, Biotechnology, and Biochemistry

Self Cite

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“…The refined structures of wild-type and R308K mutant models were subjected to MD simulations individually using NPT statistical ensemble [19] and the Nos e-Poincare-Anderson algorithm [20]. The initial temperature was set to 30 K and raised to a production phase temperature of 300 K in 100 ps with a time step of 4 fs, where the pressure was held fixed throughout the simulations with an ionic concentration of 0.145 M. The constrains were restricted to light bonds and the equations of motions made discrete with a time step of 0.002.…”

Section: Preparation and Processing Of Glucokinase Structurementioning

confidence: 99%

Conformational transition pathway of R308K mutant glucokinase in the presence of the glucokinase activator YNKGKA4

et al. 2018

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Glucokinase ( GK ) plays a vital role in the control of blood glucose levels and its altered activity can lead to the development of forms of diabetes. We have previously identified a mutant GK (R308K) in patients with type 2 diabetes with reduced enzyme activity. In the present study, the activation mechanism of GK from super‐open to the closed state under wild‐type and mutant conditions in the presence of the novel aminophosphonate derivative YNKGKA 4 (an allosteric activator of GK ) was characterized via a series of molecular dynamics simulations. A reliable conformational transition pathway of GK was observed from super‐open to closed state during trajectory analysis. Glucose was also observed to modulate its binding orientation in the active site but with stable moments in the cavity. These observations provide insights into the complicated conformational transitions in the presence of YNKGKA 4 and the molecular mechanism of GK activators for the allosteric regulation of mutant forms of GK .

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“…246 The structure of SadA has been reported, 247 and variants with altered specificity have been studied. 248 PvcB of Pseudomonas aeruginosa functions in the biosynthesis of the siderophore pyoverdine by participating in the formation of 2-isocyano-6,7-dihydroxycoumarin (reminiscent of the coumarin product shown in Figure 1.8G). The P. aeruginosa enzyme catalyses a cyclization reaction (Figure 1.10B), 249 although the mechanistic details remain obscure, and the structure of the protein has been characterized in the absence of ligands.…”

Section: Amino Acid Hydroxylasesmentioning

confidence: 99%

Biochemical Diversity of 2-Oxoglutarate-Dependent Oxygenases

Hausinger

2015

2-Oxoglutarate-Dependent Oxygenases

119

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This chapter summarizes the diverse array of biochemical transformations that are catalysed by Fe(ii)- and 2-oxoglutarate (2OG)-dependent oxygenases. One group of these enzymes utilizes protein substrates and functions in structural stabilization, oxygen sensing, histone-dependent regulation, or other roles. A second set of 2OG-dependent oxygenases acts on polynucleotides with functions that include DNA/RNA repair, regulation of transcription, biosynthesis of unique bases, and demethylation of 5-methylcytosine. A third assemblage of enzymes in this family is involved in lipid-related metabolism and function in carnitine biosynthesis, degradation of phytanic acids, and modification of various lipids. A fourth collection of these oxygenases catalyses reactions related to synthesis of flavonoids, anthocyanins, gibberellins, alkaloids and other metabolites found predominantly in plants. A fifth group of these enzymes acts on a variety of small molecules including free amino acids, nucleobases/nucleosides, herbicides, sulfonates/sulfates and phosphonates. A sixth compilation of 2OG-dependent oxygenases is utilized for antibiotic biosynthesis, including several halogenating enzymes. Finally, a seventh set of these enzymes is related in structure or mechanism to the 2OG-dependent oxygenases, but do not utilize 2OG, and include isopenicillin N synthase, a plant-specific ethylene-forming enzyme, and two enzymes that use 4-hydroxyphenylpyruvate. This introduction to the biochemical diversity of these amazing enzymes provides a foundation for appreciating the specific aspects detailed in the remaining chapters of this text.

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Structural optimization of SadA, an Fe(II)- and α-ketoglutarate-dependent dioxygenase targeting biocatalytic synthesis of N-succinyl-l-threo-3,4-dimethoxyphenylserine

Cited by 19 publications

References 18 publications

Structural analysis of enzymes used for bioindustry and bioremediation

Structural analysis of enzymes used for bioindustry and bioremediation

Conformational transition pathway of R308K mutant glucokinase in the presence of the glucokinase activator YNKGKA4

Biochemical Diversity of 2-Oxoglutarate-Dependent Oxygenases

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