Structural highlights
Publication Abstract from PubMed
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 A and 2.0 A, 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.
Crystal structures of Cg1458 reveal a catalytic lid domain and a common catalytic mechanism for FAH family.,Ran T, Gao Y, Marsh M, Zhu W, Wang M, Mao X, Xu L, Xu D, Wang W Biochem J. 2012 Oct 10. PMID:23046410[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ran T, Gao Y, Marsh M, Zhu W, Wang M, Mao X, Xu L, Xu D, Wang W. Crystal structures of Cg1458 reveal a catalytic lid domain and a common catalytic mechanism for FAH family. Biochem J. 2012 Oct 10. PMID:23046410 doi:http://dx.doi.org/10.1042/BJ20120913
