Search for fucose binding domains in recently sequenced hypothetical proteins using molecular modeling techniques and structural analysis |
| |
Authors: | Sujata Majumder Madhumita Patra Chhabinath Mandal |
| |
Institution: | (1) Drug Design, Development and Molecular Modelling Division Indian Institute of Chemical Biology Jadavpur, Kolkata, 700 032, India |
| |
Abstract: | The crystal structure of a fucose-binding lectin from the bacteria Pseudomonas aeruginosa in complex with α-L-fucose has been recently determined. It is a tetramer; each monomer displays a nine-stranded, antiparallel,
β-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. |
| |
Keywords: | Fucose-binding proteins Molecular modeling Calcium-mediated fucose binding |
本文献已被 PubMed SpringerLink 等数据库收录! |
|