Abstract
The X-ray structure of the inhibitor complex of bovine ribonuclease A with cytidylic acid (2′-CMP) has been determined at 2.3 Å (1 Å = 0.1 nm) resolution and refined by restrained least-squares refinement to
R = 0.132 for 5650 reflections. Incorporation of the inhibitor molecule has occurred with little disturbance of the protein main-chain atoms, although significant displacement of some side-chain atoms has occurred, particularly in the region of the active site. The binding of 2′-CMP to ribonuclease A is different from that of the related cytidine-
N(3)-oxide 2′-phosphate, which has an extra oxygen on N(3) of the cytidine base. The PO
4
2− group is held by hydrogen bond interactions to the side-groups of His12, Glu11 and His119. Thr45 is involved in stabilizing the enzyme-ligand complex by forming hydrogen bond interactions between O(γ) and the pyrimidine base N(3) atom and between the main-chain N(45) and O(2) of the base. Phe120 is much closer to the inhibitor than in the cytidine
N(3)-oxide 2′-phosphate structure.