X-ray refinement study on the binding of cytidylic acid (2'-CMP) to ribonuclease A.
The X-ray structure of the inhibitor complex of bovine ribonuclease A with cytidylic acid (2'-CMP) has been determined at 2.3 A (1 A = 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 PO4(2-) group is held by hydrogen bond interactions to the side-groups of His 12, Glu 11 and His119. Thr45 is involved in stabilizing the enzyme-ligand complex by forming hydrogen bond interactions between O(gamma) 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.
Howlin
B
B
Department of Crystallography, Birkbeck College, London, U.K.
Harris
G W
GW
Moss
D S
DS
Palmer
R A
RA
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D001665:Binding Sites; D003568:Cytidine Monophosphate / Q000494:pharmacology*; D003597:Cytosine Nucleotides / Q000494:pharmacology*; D008958:Models, Molecular; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors*; D014961:X-Ray Diffraction
D003597:Cytosine Nucleotides; D012259:Ribonuclease, Pancreatic; D003568:Cytidine Monophosphate