Structure of the Escherichia coli ThiS-ThiF complex, a key component of the sulfur transfer system in thiamin biosynthesis.
We have determined the crystal structure of the Escherichia coli ThiS-ThiF protein complex at 2.0 A resolution. ThiS and ThiF are bacterial proteins involved in the synthesis of the thiazole moiety of thiamin. ThiF catalyzes the adenylation of the carboxy terminus of ThiS and the subsequent displacement of AMP catalyzed by ThiI-persulfide to give a ThiS-ThiI acyl disulfide. Disulfide interchange, involving Cys184 on ThiF, then generates the ThiS-ThiF acyl disulfide, which functions as the sulfur donor for thiazole formation. ThiS is a small 7.2 kDa protein that structurally resembles ubiquitin and the molybdopterin biosynthetic protein MoaD. ThiF is a 27 kDa protein with distinct sequence and structural similarity to the ubiquitin activating enzyme E1 and the molybdopterin biosynthetic protein MoeB. The ThiF-ThiS structure clarifies the mechanism of the sulfur transfer chemistry involved in thiazole biosynthesis.
Lehmann
Christopher
C
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
Begley
Tadhg P
TP
Ealick
Steven E
SE
D000249:Adenosine Monophosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D008970:Molecular Weight; D009713:Nucleotidyltransferases / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013455:Sulfur / Q000378:metabolism*; D013466:Sulfurtransferases / Q000737:chemistry / Q000378:metabolism; D013831:Thiamine / Q000096:biosynthesis*; D013844:Thiazoles / Q000378:metabolism*; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004220:Disulfides; D029968:Escherichia coli Proteins; D013844:Thiazoles; C403342:moeB protein, Bacteria; C411655:thiS protein, E coli; D000249:Adenosine Monophosphate; D013455:Sulfur; D009713:Nucleotidyltransferases; C411654:ThiF protein, E coli; D013466:Sulfurtransferases; C491479:thiI protein, E coli; D044764:Ubiquitin-Activating Enzymes; D013831:Thiamine