Understanding human thiol dioxygenase enzymes: structure to function and biology to pathology
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Date
2017
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Abstract
Amino acid metabolism is a significant metabolic activity in humans, especially of sulphur-containing amino acids, methionine and cysteine (Cys). Cys is cytotoxic and neurotoxic in nature; hence, mammalian cells maintain a constant intracellular level of Cys. Metabolism of Cys is mainly regulated by two thiol dioxygenases: cysteine dioxygenase (CDO) and 2-aminoethanethiol dioxygenase (ADO). CDO and ADO are the only human thiol dioxygenases reported with a role in Cys metabolism and localized to mitochondria. This metabolic pathway is important in various human disorders, as it is responsible for the synthesis of antioxidant glutathione and is also
for the synthesis of hypotaurine and taurine. CDO is the most extensively studied protein, whose high-resolution crystallographic structures have been solved. As compared to CDO, ADO is less studied, even though it has a key role in cysteamine metabolism. To further understand ADO’s structure and function, the three-dimensional structures have been predicted from I-TASSER and SWISS-MODEL servers and validated with PROCHECK software. Structural superimposition approach using iPBA web server further confirmed near-identical structures (including active sites) for the predicted protein models of ADO as compared to CDO. In addition, protein–protein interaction and their association in patho-physiology are crucial in understanding protein functions. Both ADO and CDO interacting partner profiles
have been presented using STRING database. In this study, we have predicted a 3Dmodel structure for ADO and summarized the biological roles and the pathological consequences which are associated with the altered expression and functioning of ADO and CDO in case of cancer, neurodegenerative disorders and other human diseases.
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Keywords
2-Aminoethanethiol Dioxygenase, Cancer, Cupin Family, Cysteine Dioxygenase, Neurodegenerative Diseases
Citation
Sarkar, B., Kulharia, M., Mantha, AK., (2017) Understanding human thiol dioxygenase enzymes: structure to function and biology to pathology.,Volume 98, Issue 2, April 2017, Pages 52–66, DOI: 10.1111/iep.12222