Structure-function relationships in NDP-sugar active SDR enzymes : fingerprints for functional annotation and enzyme engineering
- Author
- Koen Beerens (UGent)
- Organization
- Abstract
- Short-chain Dehydrogenase/Reductase enzymes that are active on nucleotide sugars (abbreviated as NS-SDR) are of paramount importance in the biosynthesis of rare sugars and glycosides. Some family members have already been extensively characterized due to their direct implication in metabolic disorders or in the biosynthesis of virulence factors. Here, we present an in-depth analysis of all of the different NS-SDR families (169,076 enzyme sequences). Through structure-based multiple sequence alignment of enzymes retrieved from public databases, we identified clear patterns in conservation and correlation of crucial residues for each reactivity (epimerization, dehydration, reduction, decarboxylation) and known sugar specificity (e.g., UDP-galactose 4-epimerase, dTDP- glucose 4,6-dehydratase, UDP-glucuronate decarboxylase). This analysis resulted in a specificity model in which seven conserved regions surrounding the NDP-sugar substrate serve as fingerprint for each specificity: the heptagonal box model.[1] Consequently, this model will be beneficial for functional annotation of the large group of NS-SDR enzymes and form a guide for future enzyme engineering efforts focused on the biosynthesis of rare and specialty carbohydrates. To illustrate its applicability, first examples of enzyme discovery, functional annotation and enzyme engineering guided by the heptagonal box model will be presented. [1] Da Costa et al. (2020). Structure-function relationships in NDP-sugar active SDR enzymes: Fingerprints for functional annotation and enzyme engineering. Biotechnology Advances 48, 107705, DOI: 10.1016/j.biotechadv.2021.107705
- Keywords
- Specificity fingerprints, Structure-function relationship, Short-chain dehydrogenase/reductase, SDR superfamily, NDP-sugars
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8723217
- MLA
- Beerens, Koen. “Structure-Function Relationships in NDP-Sugar Active SDR Enzymes : Fingerprints for Functional Annotation and Enzyme Engineering.” ProtStab2021, 13th International Conference on Protein Stabilization, Abstracts, 2021.
- APA
- Beerens, K. (2021). Structure-function relationships in NDP-sugar active SDR enzymes : fingerprints for functional annotation and enzyme engineering. ProtStab2021, 13th International Conference on Protein Stabilization, Abstracts. Presented at the 13th International Conference on Protein Stabilization (ProtStab2021), Online.
- Chicago author-date
- Beerens, Koen. 2021. “Structure-Function Relationships in NDP-Sugar Active SDR Enzymes : Fingerprints for Functional Annotation and Enzyme Engineering.” In ProtStab2021, 13th International Conference on Protein Stabilization, Abstracts.
- Chicago author-date (all authors)
- Beerens, Koen. 2021. “Structure-Function Relationships in NDP-Sugar Active SDR Enzymes : Fingerprints for Functional Annotation and Enzyme Engineering.” In ProtStab2021, 13th International Conference on Protein Stabilization, Abstracts.
- Vancouver
- 1.Beerens K. Structure-function relationships in NDP-sugar active SDR enzymes : fingerprints for functional annotation and enzyme engineering. In: ProtStab2021, 13th International Conference on Protein Stabilization, Abstracts. 2021.
- IEEE
- [1]K. Beerens, “Structure-function relationships in NDP-sugar active SDR enzymes : fingerprints for functional annotation and enzyme engineering,” in ProtStab2021, 13th International Conference on Protein Stabilization, Abstracts, Online, 2021.
@inproceedings{8723217, abstract = {{Short-chain Dehydrogenase/Reductase enzymes that are active on nucleotide sugars (abbreviated as NS-SDR) are of paramount importance in the biosynthesis of rare sugars and glycosides. Some family members have already been extensively characterized due to their direct implication in metabolic disorders or in the biosynthesis of virulence factors. Here, we present an in-depth analysis of all of the different NS-SDR families (169,076 enzyme sequences). Through structure-based multiple sequence alignment of enzymes retrieved from public databases, we identified clear patterns in conservation and correlation of crucial residues for each reactivity (epimerization, dehydration, reduction, decarboxylation) and known sugar specificity (e.g., UDP-galactose 4-epimerase, dTDP- glucose 4,6-dehydratase, UDP-glucuronate decarboxylase). This analysis resulted in a specificity model in which seven conserved regions surrounding the NDP-sugar substrate serve as fingerprint for each specificity: the heptagonal box model.[1] Consequently, this model will be beneficial for functional annotation of the large group of NS-SDR enzymes and form a guide for future enzyme engineering efforts focused on the biosynthesis of rare and specialty carbohydrates. To illustrate its applicability, first examples of enzyme discovery, functional annotation and enzyme engineering guided by the heptagonal box model will be presented. [1] Da Costa et al. (2020). Structure-function relationships in NDP-sugar active SDR enzymes: Fingerprints for functional annotation and enzyme engineering. Biotechnology Advances 48, 107705, DOI: 10.1016/j.biotechadv.2021.107705}}, author = {{Beerens, Koen}}, booktitle = {{ProtStab2021, 13th International Conference on Protein Stabilization, Abstracts}}, keywords = {{Specificity fingerprints,Structure-function relationship,Short-chain dehydrogenase/reductase,SDR superfamily,NDP-sugars}}, language = {{eng}}, location = {{Online}}, title = {{Structure-function relationships in NDP-sugar active SDR enzymes : fingerprints for functional annotation and enzyme engineering}}, url = {{https://www.protstab2021.org/}}, year = {{2021}}, }