Document Detail

Crystal structures of Cg1458 reveal a catalytic lid domain and a common catalytic mechanism for FAH family.
MedLine Citation:
PMID:  23046410     Owner:  NLM     Status:  Publisher    
Cg1458 was recently characterized as a novel soluble oxaloacetate decarboxylase. However, sequence alignment identified that Cg1458 has no similarity with other oxaloacetate decarboxylases and instead belongs to the fumarylacetoacetate hydrolase (FAH) family. Differences in the function of Cg1458 and other FAH proteins may suggest a different catalytic mechanism. To help elucidate the catalytic mechanism of Cg1458, crystal structures of Cg1458 in both the open and closed conformations have been determined for the first time up to a resolution of 1.9 Å and 2.0 Å, respectively. Comparison of both structures and detailed biochemical studies confirmed the presence of a catalytic lid domain which is missing in the native enzyme structure. In this lid domain, a Glu-His dyad was found critical in mediating enzymatic catalysis. Based on structure modeling and comparison as well as large-scale sequence alignment studies, we further determined that the catalytic mechanism of Cg1458 is actually through a Glu-His-Water triad, and this catalytic triad is common among FAH family proteins that catalyze the cleavage of the C-C bond of the substrate. Two sequence motifs, HxxE and Hxx•••xxE have been identified as the basis for this mechanism.
Tingting Ran; Yanyan Gao; May Marsh; Wenjun Zhu; Meitian Wang; Xiang Mao; Langlai Xu; Dongqing Xu; Weiwu Wang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-10
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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