Crystal structure of microbial transglutaminase from Streptoverticillium mobaraense

Abstract

The crystal structure of a microbial transglutaminase from Streptoverticillium mobaraense has been determined at 2.4 Å resolution. The protein folds into a platelike shape, and has one deep cleft at the edge of the molecule. Its overall structure is completely different from that of the factor XIII-like transglutaminase, which possesses a cysteine protease-like catalytic triad. The catalytic residue, Cys64, exists at the bottom of the cleft. Asp255 resides at the position nearest to Cys64 and is also adjacent to His274. Interestingly, Cys64, Asp255, and His274 superimpose well on the catalytic triad "Cys-His-Asp" of the factor XIII-like transglutaminase, in this order. The secondary structure frameworks around these residues are also similar to each other. These results imply that both transglutaminases are related by convergent evolution; however, the microbial transglutaminase has developed a novel catalytic mechanism specialized for the cross-linking reaction. The structure accounts well for the catalytic mechanism, in which Asp255 is considered to be enzymatically essential, as well as for the causes of the higher reaction rate, the broader substrate specificity, and the lower deamidation activity of this enzyme.