Diamine Oxidase isoforms in placenta - structural analysis and implication in pre-eclampsia

Gyesi, Clair and Brew, Obed ORCID: https://orcid.org/0000-0003-1710-6197 (2021) Diamine Oxidase isoforms in placenta - structural analysis and implication in pre-eclampsia. Placenta, 112. e87. ISSN 0143-4004

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Objectives: Defective maternal blood Diamine Oxidase (DAO, also known as AOC1: EC: activity during trimester 1 of human pregnancy has been associated with Pre-eclampsia (PE). The enzyme is produced by the placenta to remove excess histamine produced during placentation and foetal development. The structure of the placental DAO protein was analysed for variations that could underly the defective enzyme activity in PE.

Methods: We used phylogenetic methodology to examine 41 protein sequences (NP = 21; PE = 20) extracted from RNA-Seq data to provide more accurate descriptions of patterns of relatedness and variations in conserved regions of the protein structure. We further modelled the 3D structures of each protein sample to examine conformational changes and impact on protein function in PE.

Results: We identified two types of DAO proteins in human placentae, that mapped to DAO protein isoforms P19801-1 and P19801-2 for AOC1_HUMAN held in PDB and UniProt (identity >99.5%; Expect Value = 0.0; Query Cover = 100%). Contrary to previous report that P19801-2 isoform is a non-functional protein, we isolated this isoform from a placenta with normal pregnancy outcome. There were significantly more amino acid sequence variations in the non-conserved regions of the PE than in NP proteins. Number of conserved regions’ amino acid sequence variations were similar between PE and NP proteins. There were relatively more total bonds and less angels in the PE than in NP proteins.

Conclusion: DAO protein isoform 2 was found in placenta with normal pregnancy outcome, indicating the protein has functional activity to support normal pregnancy. DAO proteins from PE placentae had more structural aberrations that could explain the defective activity observed in PE. Further work is needed to confirm the conformational changes observed in PE placental proteins

Item Type: Article
Identifier: 10.1016/j.placenta.2021.07.280
Additional Information: Abstract only
Subjects: Medicine and health
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Depositing User: Obed Brew
Date Deposited: 01 Aug 2022 13:10
Last Modified: 06 Feb 2024 16:11
URI: https://repository.uwl.ac.uk/id/eprint/9280

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