X-ray crystallographic analysis of the structural basis for the interaction of pokeweed antiviral protein with guanine residues of ribosomal RNA

Pokeweed antiviral protein (PAP) is a ribosome-inactivating protein (RIP), which enzymatically removes a single adenine base from a conserved, surface exposed loop sequence of ribosomal rRNA. We now present unprecedented expe rimental evidence that PAP can release not only adenine but guanine as well from Escherichia coli rRNA, albeit at a rate 20 times slower than for aden ine. We also report X-ray structure analysis and supporting modeling studie s for the interactions of PAP with guanine. Our modeling studies indicated that PAP can accommodate a guanine base in the active site pocket without l arge conformational changes. This prediction was experimentally confirmed, since a guanine base was visible in the active site pocket of the crystal s tructure of the PAP-guanine complex.