ESCHERICHIA-COLI CYTIDINE DEAMINASE PROVIDES A MOLECULAR-MODEL FOR APO-B RNA EDITING AND A MECHANISM FOR RNA SUBSTRATE RECOGNITION

ApoB RNA-editing enzyme (APOBEC-1) is a cytidine deaminase. Molecular modeling and mutagenesis show that APOBEC-1 is related in quaternary a nd tertiary structure to Escherichia coli cytidine deaminase (ECCDA). Both enzymes form a homodimer with composite active sites constructed with contributions from each monomer. Significant gaps are present in the APOBEC-1 sequence, compared to ECCDA. The combined mass of the gap s (10 kDa) matches that for the minimal RNA substrate. Their location in ECCDA suggests how ABOBEC-1 can be reshaped to accommodate an RNA s ubstrate. In this model, the asymmetrical binding to one active site o f a downstream U (equivalent to the deamination product) helps target the other active site for deamination of the upstream C substrate. (C) 1998 Academic Press Limited.