Anamorsin is a recently identified molecule that inhibits apoptosis during hematopoiesis. It contains an N-terminal methyltransferase-like domain and a C-terminal Fe-S cluster motif. Not much is known about the function of the protein. To better understand the function of anamorsin, we have solved the crystal structure of the N-terminal domain at 1.8 A resolution. Although the overall structure resembles a typical S-adenosylmethionine (SAM) dependent methyltransferase fold, it lacks one alpha-helix and one beta-strand. As a result, the N-terminal domain as well as the full-length anamorsin did not show S-adenosyl-l-methionine (AdoMet) dependent methyltransferase activity. Structural comparisons with known AdoMet dependent methyltransferases reveals subtle differences in the SAM binding pocket that preclude the N-terminal domain from binding to AdoMet. The N-terminal methyltransferase-like domain of anamorsin probably functions as a structural scaffold to inhibit methyl transfers by out-competing other AdoMet dependant methyltransferases or acts as bait for protein-protein interactions.Proteins 2014; 82:1066-1071. (c) 2013 Wiley Periodicals, Inc.