Open Access

Role of adenosine deaminase 2 gene variants in pediatric deficiency of adenosine deaminase 2: A structural biological approach

  • Authors:
    • Maria I. Zervou
    • George N. Goulielmos
    • Michail Matalliotakis
    • Charoula Matalliotaki
    • Demetrios A. Spandidos
    • Elias Eliopoulos
  • View Affiliations

  • Published online on: December 5, 2019     https://doi.org/10.3892/mmr.2019.10862
  • Pages: 876-882
  • Copyright: © Zervou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Adenosine deaminase 2 (ADA2) belongs to the novel family of adenosine deaminase growth factors (ADGFs), which play an important role in tissue development. The deficiency of adenosine deaminase 2 (DADA2) is a recently recognized autosomal recessive autoinflammatory disease, characterized by various systemic vascular and inflammatory manifestations, which is associated with ADA2 mutations. Considering that a recent screening of an international registry of children with systemic primary vasculitis revealed novel and already known variants in ADA2, this study aimed to further investigate the functional significance of the rare variants detected, namely p.Gly47Arg, p.Gly47Ala, p.Arg8Trp, p.Leu351Gln and p.Ala357Thr, by using a structural biological approach. Three‑dimensional models of the mutants were developed and their three‑dimensional (3D) structures were subjected to detailed interaction and conformational analyses. This led to suggestions that the novel mutations found may affect the formation/stability of the homodimer or may influence the activity of the enzyme. It was thus concluded that the Arg8Trp and Gly47Arg mutations affect the position and interaction of the dimer‑associated HN1 helical structure and therefore, dimer formation and stabilization, while Leu351Gln and Ala357Thr influence the metal coordination in the active site. These findings shed further light onto the structural consequences of the mutations under investigation.
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February 2020
Volume 21 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Zervou, M.I., Goulielmos, G.N., Matalliotakis, M., Matalliotaki, C., Spandidos, D.A., & Eliopoulos, E. (2020). Role of adenosine deaminase 2 gene variants in pediatric deficiency of adenosine deaminase 2: A structural biological approach. Molecular Medicine Reports, 21, 876-882. https://doi.org/10.3892/mmr.2019.10862
MLA
Zervou, M. I., Goulielmos, G. N., Matalliotakis, M., Matalliotaki, C., Spandidos, D. A., Eliopoulos, E."Role of adenosine deaminase 2 gene variants in pediatric deficiency of adenosine deaminase 2: A structural biological approach". Molecular Medicine Reports 21.2 (2020): 876-882.
Chicago
Zervou, M. I., Goulielmos, G. N., Matalliotakis, M., Matalliotaki, C., Spandidos, D. A., Eliopoulos, E."Role of adenosine deaminase 2 gene variants in pediatric deficiency of adenosine deaminase 2: A structural biological approach". Molecular Medicine Reports 21, no. 2 (2020): 876-882. https://doi.org/10.3892/mmr.2019.10862