Abstract
A complex of RNase A with a transition-state analog, uridine vanadate, has been studied by a combination of neutron and x-ray diffraction. The vanadium atom occupies the center of a distorted trigonal bipyramid, with the ribose oxygen O2' at the apical position. Contrary to expectations based on the straightforward interpretation of the known in-line mechanism of action of RNase, nitrogen NE2 of histidine-12 was found to form a hydrogen bond to the equatorial oxygen O8, while nitrogen NZ of lysine-41 makes a clear hydrogen bond to the apical oxygen O2'. Nitrogen ND1 of histidine-119 appears to be within a hydrogen-bond distance of the other apical oxygen, O7. Two other hydrogen bonds between the vanadate and the protein are made by nitrogen NE2 of glutamine-11 and by the amide nitrogen of phenylalanine-120. The observed geometry of the complex may necessitate reinterpretation of the mechanism of action of RNase.
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Selected References
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