Review of Fructosyl Amino Acid Oxidase Engineering Research: A Glimpse into the Future of Hemoglobin A1c Biosensing

Ferri, Stefano; Kim, Seungsu; Tsugawa, Wakako; Sode, Koji

doi:10.1177/193229680900300324

Cited by 56 publications

(36 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This structural limit has been overcome in part by the successful determination of the free and the inhibitor‐bound crystal structures of Amadoriase II from Aspergillus fumigatus, and by the more recent structure of the free fructosyl peptide oxidase from Eupenicillium terrenum (known as FPOX‐E or EtFPOD) which, to date, are the only known FAOX structures available in the literature. However, Amadoriase II has been reported to be mostly active on backbone fructosyl amines and on hydrophobic substrates (for example, glycated glycines), whereas FPOX‐E is active mostly on α‐fructosyl amino acids …”

Section: Introductionmentioning

confidence: 99%

Crystal structure of the deglycating enzyme Amadoriase I in its free form and substrate‐bound complex

et al. 2016

View full text Add to dashboard Cite

Amadoriases, also known as fructosyl amine oxidases (FAOX), are enzymes that catalyze the de-glycosylation of fructosyl amino acids. As such, they are excellent candidates for the development of enzyme-based diagnostic and therapeutic tools against age- and diabetes-induced protein glycation. However, mostly because of the lack of a complete structural characterization of the different members of the family, the molecular bases of their substrate specificity have yet to be fully understood. The high resolution crystal structures of the free and the substrate-bound form of Amadoriase I shown herein allow for the identification of key structural features that account for the diverse substrate specificity shown by this class of enzymes. This is of particular importance in the context of the rather limited and partially incomplete structural information that has so far been available in the literature on the members of the FAOX family. Moreover, using molecular dynamics simulations, we describe the tunnel conformation and the free energy profile experienced by the ligand in going from bulk water to the catalytic cavity, showing the presence of four gating helices/loops, followed by an "L-shaped" narrow cavity. In summary, the tridimensional architecture of Amadoriase I presented herein provides a reference structural framework for the design of novel enzymes for diabetes monitoring and protein deglycation. Proteins 2016; 84:744-758. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Introductionmentioning

confidence: 99%

Crystal structure of the deglycating enzyme Amadoriase I in its free form and substrate‐bound complex

et al. 2016

View full text Add to dashboard Cite

show abstract

“…As an attractive alternative to these conventional measurement systems, enzyme assay systems based on the enzyme fructosyl amino acid oxidase (FAOX) or fructosyl peptide oxidase (FPOX) have recently been commercially available. [6][7][8][9][10][11] FAOXs catalyze the oxidative degradation of fructosyl valine and/or ε-fructosyl lysine (ε-FK), which are the degradation products of HbA1c and glycated albumin, respectively ( Figure 1A). FPOXs show relatively high activity toward fructosyl valyl histidine, which corresponds to the glycosylated N-terminal dipeptide derived from HbA1c.…”

mentioning

confidence: 99%

Advancing the Development of Glycated Protein Biosensing Technology

Kameya

Sakaguchi-Mikami

Ferri

et al. 2015

J Diabetes Sci Technol

Self Cite

View full text Add to dashboard Cite

Research advances in biochemical molecules have led to the development of convenient and reproducible biosensing molecules for glycated proteins, such as those based on the enzymes fructosyl amino acid oxidase (FAOX) or fructosyl peptide oxidase (FPOX). Recently, more attractive biosensing molecules with potential applications in next-generation biosensing of glycated proteins have been aggressively reported. We review 2 such molecules, fructosamine 6-kinase (FN6K) and fructosyl amino acid-binding protein, as well as their recent applications in the development of glycated protein biosensing systems. Research on FN6K and fructosyl amino acid-binding protein has been opening up new possibilities for the development of highly sensitive and proteolytic-digestion-free biosensing systems for glycated proteins.

show abstract

“…Additionally, molecules such as ALT‐711 were developed to “break” dicarbonyl protein crosslink intermediates en route to mature AGEs; these showed favorable therapeutic effects, including a reduction in collagen crosslinking and myocardial stiffness in animal models . More recently, enzymes known as the Amadoriases and DJ‐1 have been discovered to be able to “repair” glycated proteins and nucleic acids, respectively . Although these enzymes are promising tools in AGE research, they only act on the early intermediates in glycation rather than mature AGEs.…”

Section: Introductionmentioning

confidence: 99%

Biocatalytic Reversal of Advanced Glycation End Product Modification

et al. 2019

View full text Add to dashboard Cite

Advanced glycation end products (AGEs) are a heterogeneous group of molecules that emerge from the condensation of sugars and proteins through the Maillard reaction. Despite a significant number of studies showing strong associations between AGEs and the pathologies of aging‐related illnesses, it has been a challenge to establish AGEs as causal agents primarily due to the lack of tools in reversing AGE modifications at the molecular level. Herein, we show that MnmC, an enzyme involved in a bacterial tRNA‐modification pathway, is capable of reversing the AGEs carboxyethyl‐lysine (CEL) and carboxymethyl‐lysine (CML) back to their native lysine structure. Combining structural homology analysis, site‐directed mutagenesis, and protein domain dissection studies, we generated a variant of MnmC with improved catalytic properties against CEL in its free amino acid form. We show that this enzyme variant is also active on a CEL‐modified peptidomimetic and an AGE‐containing peptide that has been established as an authentic ligand of the receptor for AGEs (RAGE). Our data demonstrate that MnmC variants are promising lead catalysts toward the development of AGE‐reversal tools and a better understanding of AGE biology.

show abstract

Review of Fructosyl Amino Acid Oxidase Engineering Research: A Glimpse into the Future of Hemoglobin A1c Biosensing

Cited by 56 publications

References 53 publications

Crystal structure of the deglycating enzyme Amadoriase I in its free form and substrate‐bound complex

Crystal structure of the deglycating enzyme Amadoriase I in its free form and substrate‐bound complex

Advancing the Development of Glycated Protein Biosensing Technology

Biocatalytic Reversal of Advanced Glycation End Product Modification

Contact Info

Product

Resources

About