Crystal structure of an enzyme involved in the biosynthesis of isoprenoids: 4-diphosphocytidyl-2C-methyl-D-erythritol kinase fromE. coli, a potential drug target
Year: 2005
Type: article
Abstract: 2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNP), a member of the 2H phosphoesterase superfamily, is firmly bound to brain white matter and found mainly in the central nervous system of vertebrates, and it catalyzes the hydrolysis of 2',3'-cyclic nucleotide to produce 2'-nucleotide.Here we report crystal structure of the catalytic fragment (CF) of human CNP (hCNP-CF) at 1.8Å resolution [1].On the basis of the present crystal structure of the hCNP-CF/phosphate complex, the available structure of the CPDase/cyclic nucleotide analogue complex, and the recent functional studies of rat CNP-CF, we propose a possible substrate-binding mode and catalytic mechanism of CNP.The proposed mechanism is basically equivalent to the second step of the well-accepted reaction mechanism of RNase A. Since the overall structure of hCNP-CF differs considerably from that of RNase A, it is likely that the similar active sites with two catalytic histidine residues in these enzymes arose through convergent evolution.
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W1975370239