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Identifying key residues of sphinganine-1-phosphate lyase for function in vivo and in vitro


Mukhopadhyay, D; Howell, K S; Riezman, H; Capitani, G (2008). Identifying key residues of sphinganine-1-phosphate lyase for function in vivo and in vitro. Journal of Biological Chemistry, 283(29):20159-20169.

Abstract

Sphinganine-1-phosphate lyase (Dpl1p) is a highly conserved enzyme of sphingolipid metabolism that catalyzes the irreversible degradation of sphingoid base phosphates, which are potent signaling molecules. Sphingoid base phosphates play a vital role in cell survival, proliferation, migration, heat stress, and cell wall integrity pathways. Little is known about the structure and regulation of Dpl1p. In this study, we have undertaken a combined computational modeling and mutagenesis approach for structure-function analysis of Dpl1p to discover possible modes of regulation. Our results identify important residues for catalysis in Dpl1p and confirm it as an integral endoplasmic reticulum-resident protein. Results further indicate that Dpl1p is most likely not regulated spatially. Importantly, we demonstrate that Dpl1p exists as an oligomer and that polar residues in its transmembrane domain are required for its full function in vivo but not for its localization or for its catalytic activity in vitro.

Abstract

Sphinganine-1-phosphate lyase (Dpl1p) is a highly conserved enzyme of sphingolipid metabolism that catalyzes the irreversible degradation of sphingoid base phosphates, which are potent signaling molecules. Sphingoid base phosphates play a vital role in cell survival, proliferation, migration, heat stress, and cell wall integrity pathways. Little is known about the structure and regulation of Dpl1p. In this study, we have undertaken a combined computational modeling and mutagenesis approach for structure-function analysis of Dpl1p to discover possible modes of regulation. Our results identify important residues for catalysis in Dpl1p and confirm it as an integral endoplasmic reticulum-resident protein. Results further indicate that Dpl1p is most likely not regulated spatially. Importantly, we demonstrate that Dpl1p exists as an oligomer and that polar residues in its transmembrane domain are required for its full function in vivo but not for its localization or for its catalytic activity in vitro.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:18 July 2008
Deposited On:18 Dec 2008 09:57
Last Modified:02 Sep 2016 07:47
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in Mukhopadhyay, D; Howell, K S; Riezman, H; Capitani, G (2008). Identifying key residues of sphinganine-1-phosphate lyase for function in vivo and in vitro. Journal of Biological Chemistry, 283(29):20159-20169. © the American Society for Biochemistry and Molecular Biology.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1074/jbc.M709753200
PubMed ID:18487605

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