Structure of epidermal growth factor

Figure 15.31. Structure of Epidermal Growth Factor. This protein growth factor is stabilized by three disulfide bonds.

Figure 14,25 Structure of epidermal growth factor. Notice that three intrachain disulfide bonds stabilize the compact three-diiTiensional structure of the growth factor, [Drawn from lEGF.pdb,]...

F/gwre (J Structure of epidermal growth factor linked at the amino-terminus to a solid surf ace. 

EGF-active factors (76), that are structurally similar to poly-APS, prevent binding of epidermal growth factors to their receptors on cell membranes, resulting in decreased DNA synthesis and cell proliferation. These compounds also bind to insulin receptors, albeit with about 10 fold lesser affinity [33]. 

Ichimatsu D, Nomura M, Nakamura S, Moritani S, Yokogawa K, Kobayashi S, Nishioka T, Miyamoto K (2007) Structure-activity relationship of flavonoids for inhibition of epidermal growth factor-induced transformation of JB6 Cl 41 cells. Mol Carcinog 46 436-445... 

These interactions involve adhesion proteins called selectins, which are found both on the rolling leukocytes and on the endothelial cells of the vascular walls. Selectins have a characteristic domain structure, consisting of an N-terminal extracellular lectin domain, a single epidermal growth factor (EGR) domain, a series of two to nine short consensus repeat (SCR) domains, a single transmembrane segment, and a short cytoplasmic domain. Lectin domains, first characterized in plants, bind carbohydrates... 

The two isozymes are both homodimers, composed of approximately 600 amino acids and possess approximately 60% homology. The three-dimensional structures of COX-1 and COX-2 are very similar. Each one consists of three independent units an epidermal growth factor-like domain, a membrane-binding section and an enzymic domain. The catalytic sites and the residues immediately adjacent are identical but for two small but crucial variations that result in an increase in the volume of the COX-2-active site, enabling it to accept inhibitor-molecules larger than those that could be accommodated in the COX-1 molecule. 

Figure 47-10. Schematic diagram of the structure of human L-selectin. The extracellular portion contains an amino terminal domain homologous to C-type lectins and an adjacent epidermal growth factor-like domain. These are followed by a variable number of complement regulatory-like modules (numbered circles) and a transmembrane sequence (blackdiamond). A short cytoplasmic sequence (open rectangle) is at the carboxyl terminal. The structures of P- and E-selectin are similar to that shown except that they contain more complement-regulatory modules.The numbers of amino acids in L-, P-, and E- selectins, as deduced from the cDNA sequences, are 385,789, and 589, respectively. (Reproduced, with permission, from Bevilacqua MP, Nelson RM Selectins. J Clin Invest 1993 91 370.)...

Nakaji-Hirabayashi T, Kato K, Iwata H (2008) Essential role of structural integrity and firm attachment of surface-anchored epidermal growth factor in adherent culture of neural stem cells. Biomaterials 29 4403 -408... 

Ogiso H, Ishitani R, Nureki O, Fukai S, Yamanaka M, Kim J-H, Saito K, Sakamoto A, Inoue M, Shirouzu M, Yokoyama S (2002) Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell 110 775-787... 

Wissner A, Overbeek E, Reich MF et al. Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (ElER-2). JMed Chem 2003 46 49-63. 

Stamos, J., Sliwkowski, M. X., Eigenbrot, C. (2002) Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol Chem 277(48), 46265-46272. 

The insulin receptor is the prototype for a number of receptor enzymes with a similar structure and receptor Tyr kinase activity. The receptors for epidermal growth factor and platelet-derived growth factor, for example, have structural and sequence similarities to the insulin receptor, and both have a protein Tyr kinase activity that phosphorylates IRS-1. Many of these receptors dimerize after binding ligand the insulin receptor is already a dimer before insulin binds. The binding of adaptor proteins such as Grb2 to (P) Tyr residues is a common mechanism for promoting protein-protein interactions, a subject to which we return in Section 12.5. 

FIGURE 1 Structures of COX-1 and COX-2, (a) COX-1 with an NSAID inhibitor (flurbiprofen, orange) bound (PDB ID 3PGH). The enzyme consists of two identical monomers (gray and blue) each with three domains a membrane anchor consisting of four amphipathic helices a second domain that somewhat resembles a domain of the epidermal growth factor and the catalytic domain, which contains the cyclooxygenase and peroxidase activities, as well as the hydrophobic channel in which the substrate (arachidonate) binds. The heme that is part of the peroxidase active sites is shown in red ... 

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