Book of Abstracts: Albany 2003Conversation 13 Abstract Book June 17-21 2003 Analysis of Structure & Function of the Ob Gene Product ? LeptinLeptin, The ob gene product, is a 16-kDa, 146 amino acid (aa) residue non ? glycosylated polypeptide. The molecule contains no consensus sites for N-linked glycosylation, but does contain two cysteines in the carboxyterminal region, both of which are belived to participate in an intramolecular disulfide linkage (1). The leptin is translated as a 167 amino acid residue polypeptide with the first 21 amino acid residues cleaved as a signal peptide. It appears therefore that changes in body fat (defined as BMI by WHO) are translated in to changes in serum leptin at the level of ob gene expression. Leptin have been found in eukaryotes and know to exhibit a higher degree of sequence homology among them (2). The crystal structure at 2.4 Å resolution of a human mutant OB protein reveals a four ? helix bundle structure. It has been our interest to study the structure ? function relationship in leptin and its correlation to body mass index in obese patients. As a preliminary step, we have compiled and analysed the amino acid sequence of leptin from 16 species and sequence similarities are compared within each segment for different species (using peptols) and the frequency of occurrence of all the 20 amino acids in these have been computed the leucine (34%) is found to be predominant among them and is highly significant as this may be important for the hydrophobic in adipose tissue. Comparison of Gene sequence of human and gorilla it has shown that there is a great deal of similarity in them, suggesting that leptin might play a similar function. Attempts have been made to study codon bias in leptin and codons from 11 species have been analyzed. While sminthopsis shows highest variation in the codon usage pattern compared to human. Less variation is observed in chimpanzee and orangutan, the details of which are discussed possibly suggesting there closeness in evolution. Biochemical studies are also underway to estimate leptin in obese subjects, the results of which are discussed.
References and Footnotes
M. Ravishankar Ram Department of Genetics |