creators_name: Kumar, Pankaj
creators_name: Singh, Mirage
creators_name: Karthikeyan, Subramanian
type: article
datestamp: 2011-12-08 18:55:49
lastmod: 2011-12-08 18:55:49
metadata_visibility: show
title: Crystal structure analysis of icosahedral lumazine synthase from Salmonella typhimurium, an antibacterial drug target.
ispublished: pub
subjects: QD
full_text_status: public
keywords: riboflavin biosynthesis; antimicrobials; FMN; FAD; pentamers; vitamin B2.
note: Copyright of this article belongs to International Union of Crystallography.

abstract: 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.
date: 2011-02
date_type: published
publication: Acta crystallographica. Section D, Biological crystallography
volume: 67
number: Pt 2
publisher: International Union of Crystallography
pagerange: 131-9
refereed: TRUE
issn: 1399-0047
official_url: http://journals.iucr.org/d/issues/2011/02/00/xb5025/xb5025.pdf
citation:   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     
document_url: http://crdd.osdd.net/open/482/1/karthi-acta-d.pdf