Biomedical subjects

Sujata Majumder

Publications and source records attributed to Sujata Majumder.

3 recordsLinked to original sources

PubMed2006

Structural studies on mannose-selective glycoprotein receptors using molecular modeling techniques.

Glycoproteins play important roles in various cellular events and their presence in appropriate locations in proper active conformations is essential for many biochemical functions. Recent evidences suggest that some glycoproteins may require sorting receptors for efficient exit from the endoplasmic reticulum. These receptors need the presence of calcium or other metal ions for their native activity. The three-dimensional structure of such a receptor, p58/ERGIC-53, has been recently solved by x-ray crystallography, which is a mannose-selective lectin and contains two Ca(2+) ions. Homology search in the sequence databases indicates a large number of proteins which bear varying degrees of homology in a wide spectrum of species with this receptor. In this study we have systematically searched for such genes which are potential candidates for acting as mannose-mediated glycoprotein receptors in various species as initially inferred from their amino acid sequence homology. Structures of a number of proteins have been predicted using knowledge-based homology modeling, and their ability to act as the glycoprotein receptor has been explored by examining the nature of sugar-binding site. Tetramer of mannose was docked in the binding pockets of the modeled structures followed by energy minimization and molecular dynamics to obtain most probable structures of the complexes. Properties of these modeled complexes were studied to examine the nature of physicochemical forces involved in the complex formation and compared with p58/ERGIC-53-mannose complex.

Amino Acid Sequence↗

PubMed2006

Search for fucose binding domains in recently sequenced hypothetical proteins using molecular modeling techniques and structural analysis.

The crystal structure of a fucose-binding lectin from the bacteria Pseudomonas aeruginosa in complex with alpha-L-fucose has been recently determined. It is a tetramer; each monomer displays a nine-stranded, antiparallel, beta-sandwiched arrangement and contains two calcium ions that mediate the binding of fucose in a recognition mode unique among protein-carbohydrate interactions. In search of this type of unique interactions in other newly discovered protein sequences, we have used molecular modeling techniques to predict and analyze the 3-D structures of some proteins, which exhibited reasonable degree of homology with the amino acid sequence of the bacterial protein. A BLAST search with the sequence of Pseudomonas aeruginosa as query in the non-redundant sequence database identified four proteins from different species, three organisms from bacteria and one from archaea. We have modeled the structures of these proteins as well as those of the complexes with carbohydrates and studied the nature of physicochemical forces involved in the complex formation both in presence and absence of calcium. The calcium-binding loops have been found to be highly conserved both in terms of primary and tertiary structures in these proteins, although a less acidic character is observed in Photorhabdus lectin due to the absence of two aspartic acid residues on the calcium-binding loop which also resulted in lower binding affinity. All these structures exhibited highly negative electrostatic environment in the vicinity of the calcium-binding loops which was essential for neutralizing the positive charges of two closely situated Ca(+2) ions. The comparison of the binding affinities of some monosaccharides other than fucose, e.g. mannose and fructose, showed higher binding energies confirming the fucose specificity of these proteins.

Amino Acid Sequence↗

PubMed2004

Prediction of 3-D structures of fucose-binding proteins and structural analysis of their interaction with ligands.

The importance of fucose-binding proteins stems from the presence of fucose as terminal sugars in H and Lewis (a) blood groups. Recently, the structure of a complex between Anguilla anguilla agglutinin (AAA) and alpha-L-fucose has been worked out at 1.9 A resolution. The structure of AAA characterizes the novel fold of an entire lectin family. In the present study, molecular modeling techniques have been used to identify new proteins that can provide a similar fucose binding module in the newly discovered genomic sequences using the above mentioned structural information. We modeled 3-D structures of three such proteins, namely, ebiP5322 protein of Anopheles gambiae, a pentraxin of Xenopus laevis, and the fw gene product of Drosophila melanogaster. alpha-L-fucose was docked in the binding pockets of the modeled structures followed by energy minimization and molecular dynamic runs to obtain the most probable structures of the complexes. Properties of these modeled complexes were studied to examine the nature of physicochemical forces involved in the complex formation and compared with AAA-alpha-L-fucose complex. It was found that ebiP5322 protein of A. gambiae and the pentraxin of X. laevis can provide a fucose-binding fold similar to AAA. We studied structures of four protein-fucose complexes to examine the electrostatic potential surfaces around the binding site and concluded that a highly positive-charged surface was not a necessary condition of fucose-binding.

Animals↗