Escherichia coli cytidine deaminase provides a molecular model for ApoB RNA editing and a mechanism for RNA substrate recognition

• Published in: Journal of molecular biology 1998-01, Vol.275 (4), p.695-714
• Main Authors: Navaratnam, N, Fujino, T, Bayliss, J, Jarmuz, A, How, A, Richardson, N, Somasekaram, A, Bhattacharya, S, Carter, C, Scott, J
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; APOBEC-1 Deaminase; Apolipoproteins B - genetics; Apolipoproteins B - metabolism; Binding Sites; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Escherichia coli - enzymology; Escherichia coli - genetics; Models, Molecular; Molecular Sequence Data; RNA Editing; RNA, Bacterial - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Substrate Specificity
• ISSN: 0022-2836
• DOI: 10.1006/jmbi.1997.1506

ApoB RNA-editing enzyme (APOBEC-1) is a cytidine deaminase. Molecular modeling and mutagenesis show that APOBEC-1 is related in quaternary and 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 gaps (10 kDa) matches that for the minimal RNA substrate. Their location in ECCDA suggests how APOBEC-1 can be reshaped to accommodate an RNA substrate. In this model, the asymmetrical binding to one active site of a downstream U (equivalent to the deamination product) helps target the other active site for deamination of the upstream C substrate.