Contrasting behavior of conformationally locked carbocyclic nucleosides of adenosine and cytidine as substrates for deaminases.
In addition to the already known differences between adenosine deaminase (ADA) and cytidine deaminase (CDA) in terms of their tertiary structure, the sphere of Zn(+2) coordination, and their reverse stereochemical preference, we present evidence that the enzymes also differ significantly in terms of the North/South conformational preferences for their substrates and the extent to which the lack of the O(4') oxygen affects the kinetics of the enzymatic deamination of carbocyclic substrates. The carbocyclic nucleoside substrates used in this study have either a flexible cyclopentane ring or a rigid bicyclo[3.1.0]hexane scaffold.
Marquez
Victor E
VE
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland, USA. marquezv@dc37a.nci.nih.gov
Schroeder
Gottfried K
GK
Ludek
Olaf R
OR
Siddiqui
Maqbool A
MA
Ezzitouni
Abdallah
A
Wolfenden
Richard
R
D000241:Adenosine / Q000737:chemistry* / Q000378:metabolism; D000243:Adenosine Deaminase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D003562:Cytidine / Q000737:chemistry* / Q000378:metabolism; D003564:Cytidine Deaminase / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation
D003562:Cytidine; D000243:Adenosine Deaminase; D003564:Cytidine Deaminase; D000241:Adenosine