title: Structure and function of allophanate hydrolase.
abstract: Allophanate hydrolase converts allophanate to ammonium and carbon dioxide. It is conserved in many organisms and is essential for their utilization of urea as a nitrogen source. It also has important functions in a newly discovered eukaryotic pyrimidine nucleic acid precursor degradation pathway, the yeast-hypha transition that several pathogens utilize to escape the host defense, and an s-triazine herbicide degradation pathway recently emerged in many soil bacteria. We have determined the crystal structure of the Kluyveromyces lactis allophanate hydrolase. Together with structure-directed functional studies, we demonstrate that its N and C domains catalyze a two-step reaction and contribute to maintaining a dimeric form of the enzyme required for their optimal activities. Our studies also provide molecular insights into their catalytic mechanism. Interestingly, we found that the C domain probably catalyzes a novel form of decarboxylation reaction that might expand the knowledge of this common reaction in biological systems.
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Fan
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Li
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Yin
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: sxiang@sibs.ac.cn.
authors.forename: Song
authors.initials: S
authors.lastname: Xiang
mesh_terms: D000492:Allophanate Hydrolase / Q000737:chemistry* / Q000378:metabolism*; D000577:Amides / Q000378:metabolism; D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003653:Decarboxylation; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D007716:Kluyveromyces / Q000201:enzymology*; D008958:Models, Molecular; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D005656:Fungal Proteins; D012996:Solutions; D000492:Allophanate Hydrolase
keywords: Allophanate Hydrolase; Amidase Signature Family; Decarboxylase; Enzyme Catalysis; Enzyme Structure; Nitrogen Metabolism; Urea Utilization; X-ray Crystallography