Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/129459
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Type: Journal article
Title: Sequence comparisons of cytochrome P450 aromatases from Australian animals predict differences in enzymatic activity and/or efficiency
Author: Fatima, A.
Holien, J.K.
Tiwari, C.
Parker, M.W.
Rodgers, R.J.
Martin, L.L.
Citation: Biology of Reproduction, 2020; 102(6):1261-1269
Publisher: Oxford University Press
Issue Date: 2020
ISSN: 0006-3363
1529-7268
Statement of
Responsibility: 
Anam Fatima, Jessica K. Holien, Chandni Tiwari, Michael W. Parker, Raymond J. Rodgers and Lisandra L. Martin
Abstract: Aromatase (P450arom, CYP19A1) is the terminal enzyme in the synthesis of the steroid hormone family of estrogens. Not surprisingly, this enzyme has structural similarities between the limited number of species studied thus far. This study examined the structure of aromatases from four diverse Australian species including a marsupial (tammar wallaby; Macropus eugenii), monotreme (platypus; Ornithorhynchus anatinus), ratite (emu; Dromaius novaehollandiae) and lizard (bearded dragon; Pogona vitticeps). We successfully built homology models for each species, using the only crystallographically determined structure available, human aromatase. The amino acid sequences showed high amino acid sequence identity to the human aromatase: wallaby 81%, platypus 73%, emu 75% and bearded dragon at 74%. The overall structure was highly conserved among the five species, although there were non-secondary structures (loops and bends) that were variable and flexible that may result in some differences in catalytic activity. At the N-terminal regions there were deletions and variations that suggest functional distinctions may be found. We found that the active sites of all these proteins were identical, except for a slight variation in the emu. The electrostatic potential across the surfaces of these aromatases highlighted likely variations to the protein-protein interactions of these enzymes with both redox partner cytochrome P450 reductase and possibly homodimerization in the case of the platypus, which has been postulated for the human aromatase enzyme. Given the high natural selection pressures on reproductive strategies the relatively high degree of conservation of aromatase sequence and structure across species suggests that there is biochemically very little scope for changes to have evolved without the loss of enzyme activity.
Keywords: Evolution of steroidogenesis; armoatase; molecular modeling; estrogen
Rights: © The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
RMID: 1000018688
DOI: 10.1093/biolre/ioaa028
Appears in Collections:Medicine publications

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