%0 Journal Article
%T C-Lobe of Lactoferrin: The Whole Story of the Half-Molecule
%A Sujata Sharma
%A Mau Sinha
%A Sanket Kaushik
%A Punit Kaur
%A Tej P. Singh
%J Biochemistry Research International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/271641
%X Lactoferrin is an iron-binding diferric glycoprotein present in most of the exocrine secretions. The major role of lactoferrin, which is found abundantly in colostrum, is antimicrobial action for the defense of mammary gland and the neonates. Lactoferrin consists of two equal halves, designated as N-lobe and C-lobe, each of which contains one iron-binding site. While the N-lobe of lactoferrin has been extensively studied and is known for its enhanced antimicrobial effect, the C-lobe of lactoferrin mediates various therapeutic functions which are still being discovered. The potential of the C-lobe in the treatment of gastropathy, diabetes, and corneal wounds and injuries has been indicated. This review provides the details of the proteolytic preparation of C-lobe, and interspecies comparisons of its sequence and structure, as well as the scope of its therapeutic applications. 1. Lactoferrin: A Bilobal Protein Lactoferrin is an iron-binding glycoprotein which is abundantly present in colostrum and is the major mediator of defence for the newborn [1¨C4]. The three-dimensional structures of lactoferrin from various species, such as human [5, 6], bovine [7, 8], buffalo [9, 10], equine [11, 12], and camel [13] have been solved. In all these cases, the overall structures of iron-saturated lactoferrin were found to have a similar folding. Lactoferrin is an 80£¿kDa single-chain glycoprotein which can be equally divided into two homologous halves, N-lobe and C-lobe, each of which is about 40£¿kDa in size and is connected to the other by a short helical segment (Figure 1). Each lobe is further subdivided into two domains, which are designated as N1 and N2 domains of N-lobe and C1 and C2 domains of C-lobe. The iron-binding site is situated inside the interdomain cleft in each lobe. The iron-binding site consists of four residues 2 tyrosines, 1 aspartate, and 1 histidine residues. The iron-binding residues in N-lobe are Asp 60, Tyr 92, Tyr 192, and His 253 while the corresponding iron-binding residues in C-lobe are Asp 395, Tyr 433, Tyr 526, and His 595. The iron-binding residues are coordinated to the ferric ion and a synergistic bidentate carbonate anion (Figure 2). Figure 1: Schematic diagram of the bovine lactoferrin molecule (PDB code: 1BLF). The N1 and N2 domains are colored in yellow and pink, respectively, while the C1 and C2 domains are colored in green and blue, respectively. The interconnecting helix between the lobes is colored in orange. The two iron atoms are shown as red spheres. Figure 2: Schematic figure of the iron-binding site of lactoferrin. The
%U http://www.hindawi.com/journals/bri/2013/271641/