The C-terminal of CysM from Mycobacterium tuberculosis protects the aminoacrylate intermediate and is involved in sulfur donor selectivity.
A new crystal structure of the dimeric cysteine synthase CysM from Mycobacterium tuberculosis reveals an open and a closed conformation of the enzyme. In the closed conformation the five carboxy-terminal amino acid residues are inserted into the active site cleft. Removal of this segment results in a decreased lifetime of the alpha-aminoacrylate reaction intermediate, an increased sensitivity to oxidants such as hydrogen peroxide, and loss of substrate selectivity with respect to the sulfur carrier thiocarboxylated CysO. These results highlight features of CysM that might be of particular importance for cysteine biosynthesis under oxidative stress in M. tuberculosis.
Agren
Daniel
D
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles vg 2, S-171 77 Stockholm, Sweden.
Schnell
Robert
R
Schneider
Gunter
G
D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000096:biosynthesis*; D003547:Cysteine Synthase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008956:Models, Chemical; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D018384:Oxidative Stress; D011487:Protein Conformation; D013455:Sulfur / Q000378:metabolism*
D013455:Sulfur; C015102:dehydroalanine; D006861:Hydrogen Peroxide; D003547:Cysteine Synthase; D003545:Cysteine; D000409:Alanine