Biomedical subjects

Shoba Ranganathan

Publications and source records attributed to Shoba Ranganathan.

5 recordsLinked to original sources

PubMed2003

MGAlignIt: A web service for the alignment of mRNA/EST and genomic sequences.

Splicing is a biological phenomenon that removes the non-coding sequence from the transcripts to produce a mature transcript suitable for translation. To study this phenomenon, information on the intron-exon arrangement of a gene is essential, usually obtained by aligning mRNA/EST sequences to their cognate genomic sequences. MGAlign is a novel, rapid, memory efficient and practical method for aligning mRNA/EST and genome sequences. We present here a freely available web service, MGAlignIt (http://origin.bic.nus.edu.sg/mgalign/mgalignit), based on MGAlign. Besides the alignment itself, this web service allows users to effectively visualize the alignment in a graphical manner and to perform limited analysis on the alignment output. The server also permits the alignment to be saved in several forms, both graphical and text, suitable for further processing and analysis by other programs.

Algorithms↗

PubMed2003

MPID: MHC-Peptide Interaction Database for sequence-structure-function information on peptides binding to MHC molecules.

SUMMARY: Binding of short antigenic peptides to Major histocompatibility complex (MHC) proteins is the first step in T-cell mediated immune response. To understand the structural principles governing MHC-specific peptide recognition and binding, we have developed the MHC-Peptide Interaction Database (MPID), containing sequence-structure-function information. MPID (version 1.2) contains curated x-ray crystallographic data on 86 MHC peptide complexes, with precomputed interaction parameters (solvent accessibility, hydrogen bonds, gap volume and gap index). A user-friendly web interface and query tools will facilitate the development of predictive algorithms for MHC-peptide binding from a structural viewpoint. AVAILABILITY: Freely accessible from http://surya.bic.nus.edu.sg/mpid.

Binding Sites↗

PubMed2003

A common site within factor H SCR 7 responsible for binding heparin, C-reactive protein and streptococcal M protein.

The complement inhibitor factor H (fH) interacts via its seventh short consensus repeat (SCR) domain with multiple ligands including heparin, streptococcal M protein and C-reactive protein (CRP). The aim of this study was to localize the residues in SCR 7 required for these interactions. We initially built a homology model of fH SCR 6-7 using the averaged NMR structures of fH SCR 15-16 and vaccinia control protein SCR 3-4 as templates. Electrostatic potentials of the model's surface demonstrated a co-localization of three clusters of positively charged residues on SCR 7, labeled site A (R369 and K370), site B (R386 and K387) and site C (K392). These residues, localized to the linker region preceding SCR 7 and to the end of a "hypervariable loop" in SCR 7, were systematically replaced with uncharged alanine residues in an fH construct containing SCR 1-7. The resulting proteins were expressed in the methylotrophic yeast, Pichia pastoris. By ELISA analysis we demonstrated: first, that substituting site A inhibited heparin and CRP binding; secondly, that substituting site B inhibited binding to heparin, CRP and M protein; and thirdly, that substituting site C clearly inhibited only heparin binding.

Amino Acid Substitution↗

PubMed2003

XdomView: protein domain and exon position visualization.

SUMMARY: The relationship between intron distribution in the eukaryotic gene and protein structural elements is essential for understanding the origin and evolution of genes. XdomView is a web-based viewer mapping protein structural domains and intron positions in eukaryotic homologues to its tertiary structure. The association of sequence signals to 3D structure in XdomView provides a valuable visualization environment for eukaryotic gene organization, gene evolution, protein folding and protein structure classification. AVAILABILITY: Freely available from http://surya.bic.nus.edu.sg/xdom.

Database Management Systems↗

PubMed2002

kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity.

An important and exciting challenge in the postgenomic era is to understand the functions of newly discovered proteins based on their structures. The main thrust is to find the common structural motifs that contribute to specific functions. Using this premise, here we report the purification, solution NMR, and functional characterization of a novel class of weak potassium channel toxins from the venom of the scorpion Heterometrus fulvipes. These toxins, kappa-hefutoxin1 and kappa-hefutoxin2, exhibit no homology to any known toxins. NMR studies indicate that kappa-hefutoxin1 adopts a unique three-dimensional fold of two parallel helices linked by two disulfide bridges without any beta-sheets. Based on the presence of the functional diad (Tyr(5)/Lys(19)) at a distance (6.0 +/- 1.0 A) comparable with other potassium channel toxins, we hypothesized its function as a potassium channel toxin. kappa-Hefutoxin 1 not only blocks the voltage-gated K(+)-channels, Kv1.3 and Kv1.2, but also slows the activation kinetics of Kv1.3 currents, a novel feature of kappa-hefutoxin 1, unlike other scorpion toxins, which are considered solely pore blockers. Alanine mutants (Y5A, K19A, and Y5A/K19A) failed to block the channels, indicating the importance of the functional diad.

Amino Acid Sequence↗