The nucleoside deaminases for cytidine and adenosine: structure, transition state stabilization, mechanism, and evolution.
Enzymatic deamination of cytidine and adenosine bases in RNA have recently been shown to be mechanisms for changing the coding specificity of messenger and transfer RNAs. The structures of the enzymes that carry out deamination of the corresponding nucleosides have been analyzed by X-ray crystallography. They are quite different from one another in most respects, including quaternary and tertiary structure, but they have similar chemical groups in their active sites. Both enzymes envelope their nucleoside substrates completely, perhaps accounting for the fact that they are inactive on RNA substrates. Much has been learned about catalytic mechanisms from the structures of the enzymes and their complexes with transition state analog inhibitors. Catalysis proceeds with the activation by zinc of a bound water molecule, presumably to hydroxide ion, which attacks the appropriate carbon to generate a tetrahedral intermediate. The detailed stereochemistry of the two resulting chiral centers is diastereoisomeric. Details of the ensuing proton transfer steps necessary to generate and release the products are also apparently different in the two enzymes. Thus, the active site similarities are probably the result of convergent evolution.
Carter
C W
CW
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill 27599-7260, USA.
D000243:Adenosine Deaminase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D005075:Biological Evolution; D003564:Cytidine Deaminase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000378:metabolism
D008024:Ligands; D000243:Adenosine Deaminase; D003564:Cytidine Deaminase; D015032:Zinc