Structural Analysis of Saccharomyces cerevisiae Dihydroorotase Reveals Molecular Insights into the Tetramerization Mechanism

doi:10.3390/molecules26237249

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23896

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23896

Title:	Structural Analysis of Saccharomyces cerevisiae Dihydroorotase Reveals Molecular Insights into the Tetramerization Mechanism
Authors:	Guan, HH;Huang, YH;Lin, ES;Chen, CJ;Huang, CY
Keywords:	dihydroorotase;tetramerization;pyrimidine biosynthesis;CAD;dihydropyrimidinase;allantoinase;thermostability
Date:	2021
Issue Date:	2022-08-05T09:44:36Z (UTC)
Publisher:	MDPI
Abstract:	Dihydroorotase (DHOase), a dimetalloenzyme containing a carbamylated lysine within the active site, is a member of the cyclic amidohydrolase family, which also includes allantoinase (ALLase), dihydropyrimidinase (DHPase), hydantoinase, and imidase. Unlike most known cyclic amidohydrolases, which are tetrameric, DHOase exists as a monomer or dimer. Here, we report and analyze two crystal structures of the eukaryotic Saccharomyces cerevisiae DHOase (ScDHOase) complexed with malate. The structures of different DHOases were also compared. An asymmetric unit of these crystals contained four crystallographically independent ScDHOase monomers. ScDHOase shares structural similarity with Escherichia coli DHOase (EcDHOase). Unlike EcDHOase, ScDHOase can form tetramers, both in the crystalline state and in solution. In addition, the subunit-interacting residues of ScDHOase for dimerization and tetramerization are significantly different from those of other DHOases. The tetramerization pattern of ScDHOase is also different from those of DHPase and ALLase. Based on sequence analysis and structural evidence, we identify two unique helices (alpha 6 and alpha 10) and a loop (loop 7) for tetramerization, and discuss why the residues for tetramerization in ScDHOase are not necessarily conserved among DHOases.
URI:	http://dx.doi.org/10.3390/molecules26237249 https://www.webofscience.com/wos/woscc/full-record/WOS:000734508700001 https://ir.csmu.edu.tw:8080/handle/310902500/23896
Relation:	MOLECULES ,2021,v26,issue 23
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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