title: Specific interactions of C-terminal half (C-lobe) of lactoferrin protein with edible sugars: binding and structural studies with implications on diabetes.
abstract: Bovine lactoferrin has been shown to reduce the levels of glucose in both normal subjects and non-insulin dependent diabetic patients. The binding studies have shown that various sugar molecules interact with lactoferrin indicating the presence of a sugar-binding site in the protein. Structural studies have revealed that the sugar-binding site is located in the C-terminal half (C-lobe) of bilobal lactoferrin. Since the sugar-binding site was part of the C-lobe, it was better to carry out binding and structural studies using C-lobe rather than the full protein molecule. Therefore, C-lobe was prepared by limited proteolysis of lactoferrin with enzyme proteinase K. It was purified to homogeneity for further studies. The addition of C-lobe to human serum showed significant lowering of glucose levels. The binding studies using C-lobe with nine sugars, glucose, galactose, mannose, xylose, maltose, cellobiose, lactose, sucrose and dextrin gave values of binding constants in the range of 10(-4) to 10(-5)M. The structure determinations of the complexes of C-lobe with all the nine sugars showed that all of them interact with C-lobe through the same recognition site involving several hydrogen bonds and van der Waals interactions.
authors.affiliation: Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Rafia
authors.initials: R
authors.lastname: Mir
authors.forename: Ramasamy Prem
authors.initials: RP
authors.lastname: Kumar
authors.forename: Nagendra
authors.initials: N
authors.lastname: Singh
authors.forename: Gopalakrishna Pillai
authors.initials: GP
authors.lastname: Vikram
authors.forename: Mau
authors.initials: M
authors.lastname: Sinha
authors.forename: Asha
authors.initials: A
authors.lastname: Bhushan
authors.forename: Punit
authors.initials: P
authors.lastname: Kaur
authors.forename: Alagiri
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Sujata
authors.initials: S
authors.lastname: Sharma
authors.forename: Tej P
authors.initials: TP
authors.lastname: Singh
mesh_terms: D000818:Animals; D002417:Cattle; D019422:Dietary Sucrose / Q000737:chemistry*; D019286:Endopeptidase K / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D007781:Lactoferrin / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D019422:Dietary Sucrose; D007781:Lactoferrin; D019286:Endopeptidase K