2013 Fiscal Year Final Research Report
Crystal structure of the extracellular glycoprotein Enpp1
| Project/Area Number |
23687014
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Structural biochemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NISHIMASU Hiroshi 東京大学, 理学(系)研究科(研究院), 助教 (00467044)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | Enpp / 骨形成 / X線結晶構造 / 細胞外酵素 |
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| Research Abstract |
Enpp1 is a membrane-bound glycoprotein that regulates bone mineralization by hydrolyzing extracellular nucleotide triphosphates to produce pyrophosphate. Enpp1 dysfunction causes human diseases characterized by ectopic calcification. Enpp1 also inhibits insulin signaling, and an Enpp1 polymorphism is associated with insulin resistance. However, the precise mechanism by which Enpp1 functions in these cellular processes remains elusive. Here, we report the crystal structures of the extracellular region of mouse Enpp1 in complex with four different nucleotide monophosphates. Structural mapping of disease-associated mutations indicated the functional importance of the interdomain interactions. A structural comparison of Enpp1 with Enpp2, a lysophospholipase D, revealed marked differences in the domain arrangements and active-site architectures. Our findings provide structural insights into how the Enpp family proteins evolved to exert their diverse cellular functions.
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[Journal Article] Structural basis for potent inhibition of SIRT2 deacetylase by a macrocyclic peptide inducing dynamic structural change2014
Author(s)
Yamagata K, Goto Y, Nishimasu H, Morimoto J, Ishitani R, Dohmae N, Takeda N, Nagai R, Komuro I, Suga H, Nureki O
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Journal Title
Structure
Volume: 22(2)
Pages: 345-352
DOI
Peer Reviewed
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[Journal Article] Structure and function of Zucchini endoribonuclease in piRNA biogenesis2012
Author(s)
Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK, Bonnefond L, Matsumoto N, Nishizawa T, Nakanaga K, Aoki J, Ishitani R, Siomi H, Siomi MC, Nureki O
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Journal Title
Nature
Volume: 491(7423)
Pages: 284-287
DOI
Peer Reviewed
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