Crystal structure analysis of icosahedral lumazine synthase from Salmonella typhimurium, an antibacterial drug target.
Riboflavin biosynthesis is an essential pathway in bacteria, in contrast to animals, which obtain riboflavin from their diet. Therefore, the enzymes involved in the riboflavin-biosynthesis pathway are potential targets for the development of antibacterial drugs. Lumazine synthase, an enzyme that is involved in the penultimate step of riboflavin biosynthesis, catalyzes the formation of 6,7-dimethyl-8-ribityllumazine from 3,4-dihydroxy-2-butanone 4-phosphate and 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione. Lumazine synthase from Salmonella typhimurium (sLS) has been cloned, overexpressed, purified and was crystallized in three forms, each with different crystal packing. The crystal structure of sLS in the monoclinic space group P2(1) has been determined with 60 subunits per asymmetric unit, packed as an icosahedron, at 3.57 Å resolution. Interestingly, sLS contains an N-terminal proline residue (Pro11) which had previously been suggested to disrupt the formation of the icosohedral assembly. In addition, comparison of the structure of sLS with known orthologous lumazine synthase structures allowed identification of the amino-acid residues involved in substrate binding and catalysis. The sLS structure reported here could serve as a starting point for the development of species-specific antibacterial drugs.
Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39-A, Chandigarh 160 036, India.
Pankaj
P
Kumar
Mirage
M
Singh
Subramanian
S
Karthikeyan
D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D015870:Gene Expression; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012486:Salmonella typhimurium / Q000201:enzymology*; D016415:Sequence Alignment; D013379:Substrate Specificity
D009097:Multienzyme Complexes; C044822:6,7-dimethyl-8-ribityllumazine synthase