Vyas, R.; Tewari, R.; Weiss, M.S.; Karthikeyan, S.: Structures of ternary complexes of aspartate-semialdehyde dehydrogenase (Rv3708c) from Mycobacterium tuberculosis H37Rv. Acta Crystallographica Section D - Biological Crystallography 68 (2012), p. 671-679

resolution and in complex with S-methyl-l-cysteine sulfoxide (SMCS) and sulfate at 1.95 A resolution. The overall structure of Mtb-ASADH is similar to those of its orthologues. However, in the Mtb-ASADH–glycerol complex structure the glycerol molecule is noncovalently bound to the active-site residue Cys130, while in the Mtb-ASADH–SMCS complex structure the SMCS (Cys) is covalently linked to Cys130. The Mtb-ASADH–SMCS complex structurally mimics one of the intermediate steps in the proposed mechanism of ASADH enzyme catalysis. Comparison of the two complex structures revealed that the amino acids Glu224 and Arg249 undergo conformational changes upon binding of glycerol. Moreover, the structures reported here may help in the development of species-specific antibacterial drug molecules against human pathogens.