Structure and mechanism of ADP-ribose-1''-monophosphatase (Appr-1''-pase), a ubiquitous cellular processing enzyme.
Appr-1''-pase, an important and ubiquitous cellular processing enzyme involved in the tRNA splicing pathway, catalyzes the conversion of ADP-ribose-1''monophosphate (Appr-1''-p) to ADP-ribose. The structures of the native enzyme from the yeast and its complex with ADP-ribose were determined to 1.9 A and 2.05 A, respectively. Analysis of the three-dimensional structure of this protein, selected as a target in a structural genomics project, reveals its putative function and provides clues to the catalytic mechanism. The structure of the 284-amino acid protein shows a two-domain architecture consisting of a three-layer alphabetaalpha sandwich N-terminal domain connected to a small C-terminal helical domain. The structure of Appr-1''-pase in complex with the product, ADP-ribose, reveals an active-site water molecule poised for nucleophilic attack on the terminal phosphate group. Loop-region residues Asn 80, Asp 90, and His 145 may form a catalytic triad.
Kumaran
Desigan
D
Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Eswaramoorthy
Subramaniam
S
Studier
F William
FW
Swaminathan
Subramanyam
S
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D015003:Yeasts / Q000201:enzymology
C496852:ADP-ribose 1''-phosphate; D029701:Saccharomyces cerevisiae Proteins; D000246:Adenosine Diphosphate Ribose; C501455:ADP-ribose-1''-monophosphatase, S cerevisiae; D010744:Phosphoric Monoester Hydrolases
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