In most living organisms, urea is generated in the degradation of nitrogen-containing molecules. In mammals, urea is excreted and is the main nitrogen-containing compound in the urine. Plants, fungi, algae, and bacteria possess an enzymatic activity that converts urea to ammonium, enabling them to utilize urea as a nitrogen source. Two distinct enzymes catalyze the conversion of urea toammonium: the nickel-containing enzyme urease and the biotin-dependent enzyme urea amidolyase. Urea amidolyase is composed of urea carboxylase (UC) and allophanate hydrolase (AH) activities. UC coverts urea to allophanate, and AH subsequently converts it to ammonium.
A team of researchers, led by Professor XIANG Song, at the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (INS), has determined the crystal structure of Urea Carboxylase (UC). This work provides insights into the UC carboxyltransfer reaction.
Urea Carboxylase belongs to the biotin-dependent carboxylase superfamily, and is composed of biotin carboxylase (BC),carboxyltransferase (CT) and biotin carboxyl carrier protein (BCCP) domains. The BC and CT domains catalyze the first and second steps of the UC reaction: carboxylation of biotin and transfer of the carboxyl group from biotin to urea, respectively; and biotin is covalently linked to the BCCP domain. Structural and sequence analyses indicate the CT domain belongs to a large family of proteins with diverse functions, including the Bacillus subtilis KipA-KipI complex, which play important roles in sporulation regulation. A structure of the KipA-KipI complex is currently not available, and the structure of the UC CT domain provides insights into its function. Most interestingly, the structure captured the conformation in which the BCCP domain binds to the CT domain and delivers biotin into its active site. This structural information and follow-up biochemical experiments revealed the molecular mechanism of the UC carboxyltransfer reaction.
The related paper entitled "Crystal Structure of Urea Carboxylase Provides Insights into the Carboxyltransfer Reaction" was published in The Journal of Biological Chemistry on January 25, 2012.
Contact:
SONG Xiang
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
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