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Crystal structure analysis of icosahedral lumazine synthase from Salmonella typhimurium, an antibacterial drug target.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Crystal structure analysis of icosahedral lumazine synthase from Salmonella typhimurium, an antibacterial drug target.
 
Creator Kumar, Pankaj
Singh, Mirage
Karthikeyan, Subramanian
 
Subject QD Chemistry
 
Description 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.
 
Publisher International Union of Crystallography
 
Date 2011-02
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/482/1/karthi-acta-d.pdf
Kumar, Pankaj and Singh, Mirage and Karthikeyan, Subramanian (2011) Crystal structure analysis of icosahedral lumazine synthase from Salmonella typhimurium, an antibacterial drug target. Acta crystallographica. Section D, Biological crystallography, 67 (Pt 2). pp. 131-9. ISSN 1399-0047
 
Relation http://journals.iucr.org/d/issues/2011/02/00/xb5025/xb5025.pdf
http://crdd.osdd.net/open/482/