The active Site of Ribonuclease A from the Crystallographic Studies of Ribonuclease‐A‐Inhibitor Complexes

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Abstract
The results of X‐ray analyses of three ribonuclase‐A‐nucleotide complexes, at 2.3 Å, are reproted, A modified purine mononucleotide, 8‐oxo‐guanosine 2′‐phosphate in a synconformation binds at the pyrimidine‐binding site of the catalytic cleft. Solvent molecules are expelled from the active site due to inhibitor binding. The positions of the side‐chains of the active‐site residues Gln‐11, His‐12 and Thr‐45 are well defined and do not alter on inhibitor binding. The mobility of Lys‐41 is greatly reduced in protein‐nucleotde complexes and the terminal amino group interacts directly, with the 2′‐phosphate group of the nucleotides. In the complex of the enzyme with a modified pyrimidine, cytidine‐N(3)‐oxide 2′‐phosphate, His‐119 is stabilised in the minor site of the native protein [Borkakoti, N., M, D. S. and Palmer, R. A. (1982) Acta Crystallogr. B38, 2210–2217], while in the protein‐purine derivative the imidazole group is located in the major site. Inhibitor binding induces movements in the site‐chains of Lys‐7 and Lys‐66 which also modify the conformation of the active‐site cleft of ribonuclease A.

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