Next Article in Journal
Brain Vascular Microenvironments in Cancer Metastasis
Next Article in Special Issue
Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis
Previous Article in Journal
Evidence for Enhanced Efficacy of Passive Immunotherapy against Beta-Amyloid in CD33-Negative 5xFAD Mice
Previous Article in Special Issue
The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients
 
 
Article

Structural Analysis of the Effect of Asn107Ser Mutation on Alg13 Activity and Alg13-Alg14 Complex Formation and Expanding the Phenotypic Variability of ALG13-CDG

1
Tunneling Group, Biotechnology Centre, Silesian University of Technology, 44-100 Gliwice, Poland
2
Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children’s Memorial Health Institute, 04-736 Warsaw, Poland
3
Anthropology Laboratory, Children’s Memorial Health Institute, 04-736 Warsaw, Poland
4
Department of Pediatrics, Nutrition and Metabolic Disorders, Children’s Memorial Health Institute, 04-736 Warsaw, Poland
5
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland
*
Authors to whom correspondence should be addressed.
Academic Editor: Hassan Y. Naim
Biomolecules 2022, 12(3), 398; https://doi.org/10.3390/biom12030398
Received: 16 October 2021 / Accepted: 2 March 2022 / Published: 4 March 2022
Congenital Disorders of Glycosylation (CDG) are multisystemic metabolic disorders showing highly heterogeneous clinical presentation, molecular etiology, and laboratory results. Here, we present different transferrin isoform patterns (obtained by isoelectric focusing) from three female patients harboring the ALG13 c.320A>G mutation. Contrary to other known variants of type I CDGs, where transferrin isoelectric focusing revealed notably increased asialo- and disialotransferrin fractions, a normal glycosylation pattern was observed in the probands. To verify this data and give novel insight into this variant, we modeled the human Alg13 protein and analyzed the dynamics of the apo structure and the complex with the UDP-GlcNAc substrate. We also modeled the Alg13-Alg14 heterodimer and ran multiple simulations of the complex in the presence of the substrate. Finally, we proposed a plausible complex formation mechanism. View Full-Text
Keywords: ALG13-CDG; c.320A>G variant (p.Asn107Ser); congenital disorder of glycosylation; transferrin isoelectric focusing; human Alg13 modeling ALG13-CDG; c.320A>G variant (p.Asn107Ser); congenital disorder of glycosylation; transferrin isoelectric focusing; human Alg13 modeling
Show Figures

Figure 1

MDPI and ACS Style

Mitusińska, K.; Góra, A.; Bogdańska, A.; Rożdżyńska-Świątkowska, A.; Tylki-Szymańska, A.; Jezela-Stanek, A. Structural Analysis of the Effect of Asn107Ser Mutation on Alg13 Activity and Alg13-Alg14 Complex Formation and Expanding the Phenotypic Variability of ALG13-CDG. Biomolecules 2022, 12, 398. https://doi.org/10.3390/biom12030398

AMA Style

Mitusińska K, Góra A, Bogdańska A, Rożdżyńska-Świątkowska A, Tylki-Szymańska A, Jezela-Stanek A. Structural Analysis of the Effect of Asn107Ser Mutation on Alg13 Activity and Alg13-Alg14 Complex Formation and Expanding the Phenotypic Variability of ALG13-CDG. Biomolecules. 2022; 12(3):398. https://doi.org/10.3390/biom12030398

Chicago/Turabian Style

Mitusińska, Karolina, Artur Góra, Anna Bogdańska, Agnieszka Rożdżyńska-Świątkowska, Anna Tylki-Szymańska, and Aleksandra Jezela-Stanek. 2022. "Structural Analysis of the Effect of Asn107Ser Mutation on Alg13 Activity and Alg13-Alg14 Complex Formation and Expanding the Phenotypic Variability of ALG13-CDG" Biomolecules 12, no. 3: 398. https://doi.org/10.3390/biom12030398

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop