Structure of a coenzyme A pyrophosphatase from Deinococcus radiodurans: a member of the Nudix family.
Gene Dr1184 from Deinococcus radiodurans codes for a Nudix enzyme (DR-CoAse) that hydrolyzes the pyrophosphate moiety of coenzyme A (CoA). Nudix enzymes with the same specificity have been found in yeast, humans, and mice. The three-dimensional structure of DR-CoAse, the first of a Nudix hydrolase with this specificity, reveals that this enzyme contains, in addition to the fold observed in other Nudix enzymes, insertions that are characteristic of a CoA-hydrolyzing Nudix subfamily. The structure of the complex of the enzyme with Mg(2+), its activating cation, reveals the position of the catalytic site. A helix, part of the N-terminal insertion, partially occludes the binding site and has to change its position to permit substrate binding. Comparison of the structure of DR-CoAse to those of other Nudix enzymes, together with the location in the structure of the sequence characteristic of CoAses, suggests a mode of binding of the substrate to the enzyme that is compatible with all available data.
Kang
Lin-Woo
LW
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Gabelli
Sandra B
SB
Bianchet
Mario A
MA
Xu
Wen Lian
WL
Bessman
Maurice J
MJ
Amzel
L Mario
LM
D000595:Amino Acid Sequence; D001665:Binding Sites; D002413:Cations, Divalent / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism*; D018360:Crystallography, X-Ray; D034301:Deinococcus / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011755:Pyrophosphatases / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity
D002413:Cations, Divalent; D011755:Pyrophosphatases; D003065:Coenzyme A