Functional correlation of bacterial LuxS with their quaternary associations: interface analysis of the structure networks.
BACKGROUND
The genome of a wide variety of prokaryotes contains the luxS gene homologue, which encodes for the protein S-ribosylhomocysteinelyase (LuxS). This protein is responsible for the production of the quorum sensing molecule, AI-2 and has been implicated in a variety of functions such as flagellar motility, metabolic regulation, toxin production and even in pathogenicity. A high structural similarity is present in the LuxS structures determined from a few species. In this study, we have modelled the structures from several other species and have investigated their dimer interfaces. We have attempted to correlate the interface features of LuxS with the phenotypic nature of the organisms.


RESULTS
The protein structure networks (PSN) are constructed and graph theoretical analysis is performed on the structures obtained from X-ray crystallography and on the modelled ones. The interfaces, which are known to contain the active site, are characterized from the PSNs of these homodimeric proteins. The key features presented by the protein interfaces are investigated for the classification of the proteins in relation to their function. From our analysis, structural interface motifs are identified for each class in our dataset, which showed distinctly different pattern at the interface of LuxS for the probiotics and some extremophiles. Our analysis also reveals potential sites of mutation and geometric patterns at the interface that was not evident from conventional sequence alignment studies.


CONCLUSIONS
The structure network approach employed in this study for the analysis of dimeric interfaces in LuxS has brought out certain structural details at the side-chain interaction level, which were elusive from the conventional structure comparison methods. The results from this study provide a better understanding of the relation between the luxS gene and its functional role in the prokaryotes. This study also makes it possible to explore the potential direction towards the design of inhibitors of LuxS and thus towards a wide range of antimicrobials.
Bhattacharyya
Moitrayee
M
Molecular Biophysics Unit, Indian Institute of Science, Bangalore - 560012, India. moitrayee@mbu.iisc.ernet.in
Vishveshwara
Saraswathi
S
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics*; D013437:Carbon-Sulfur Lyases / Q000737:chemistry* / Q000235:genetics*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D055503:Protein Multimerization; D016415:Sequence Alignment
D001426:Bacterial Proteins; D050505:Mutant Proteins; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria