Influence of naturally-occurring 5'-pyrophosphate-linked substituents on the binding of adenylic inhibitors to ribonuclease a: an X-ray crystallographic study.

ABSTRACT: Ribonuclease A is the archetype of a functionally diverse superfamily of vertebrate-specific ribonucleases. Inhibitors of its action have potential use in the elucidation of the in vivo roles of these enzymes and in the treatment of pathologies associated therewith. Derivatives of adenosine 5'-pyrophosphate are the most potent nucleotide-based inhibitors known. Here, we use X-ray crystallography to visualize the binding of four naturally-occurring derivatives that contain 5'-pyrophosphate-linked extensions. 5'-ATP binds with the adenine occupying the B(2) subsite in the manner of an RNA substrate but with the gamma-phosphate at the P(1) subsite. Diadenosine triphosphate (Ap(3)A) binds with the adenine in syn conformation, the beta-phosphate as the principal P(1) subsite ligand and without

SUBMITTER: Holloway DE 

PROVIDER: S-EPMC2816359 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature