Hedgehog proteins

Calcutt, N. A., Allendoerfer, K. L., Mizisin, A. P. et al. Therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy. /. Clin. Invest. Ill 507-514,2003. 

The C-terminal steroid-modified heptapeptides, corresponding to the C-terminus of Hedgehog proteins, were synthesized in a combined solid-/solution-phase approach. The strategy was based on a dipeptide. 

The C-terminal steroid modified heptapeptides, corresponding to the C-terminus of Hedgehog proteins, were synthesized in a combined solid-phase/solntion approach (41). The synthesis built on the dipeptide Fmoc-SG-OAU that was connected to the trityl resin via the free hydroxyl fnnctionality of the serine. The C -terminal allyl ester was cleaved by noble-metal-mediated... 

Peters C, Wolf A, Wagner M, Kuhlmann J, Waldmann H. The cholesterol membrane anchor of the Hedgehog protein confers stable membrane association to lipid-modified proteins. Proc. Natl. Acad. Sci. U.S.A. 2004 101 8531-8536. 

Peptide mapping of the Sonic Hedgehog protein (SHH) was done via a cyanogen bromide (CNBr) digest that cleaved at the carboxy-terminus of Methionine residues (12). The SHH protein was in a... 

Fig. 4 Cyanogen Bromide Digest of Sonic Hedgehog Protein.

Haversian system, 530 HDl-s [high-density lipoproteins), 312,332 altaied by diel, 363 apo A-1,336,339-340 apo A-ll, 336 apo C-U, 337 apo E, 337-33S in bloodstream, 343-344 cardiovascular disease and, 370 cyding of cholestErol and, 339 343 Maditeiranean diet 364-365 Heart attack, 360 Heat stroke. 699 Hedgehog (protein), 326 Helicobacter pylori, 87 Helper phage, 951 Heme... 

In addition to Its structural role In membranes, discussed In Chapter 5, cholesterol Is the precursor for several Important bloactive molecules. They Include bile acids (see Figure 18-6), which are made In the liver and help emulsify dietary fats for digestion and absorption In the Intestines, steroid hormones produced by endocrine cells (e.g., adrenal gland, ovary, testes), and vitamin D produced In the skin and kidneys. Arthropods need cholesterol or other sterols to produce membranes and ecdysterold hormones, which control development however, they cannot make the precursor sterols themselves and must obtain these compounds In their diet. Another critical function of cholesterol Is Its covalent addition to Hedgehog protein, a key signaling molecule In embryonic development (Chapter 15). 

Fig. (14). Intramolecular autoprocessing reactions of Sonic hedgehog proteins.

Palmitoylation, the addition of 16 0 to a protein, is also commonly observed. This modification to the sulfydryl side chain of cysteine residues occurs post-translationally and is reversible. Both membrane-associated proteins and integral membrane proteins can be palmitoylated examples are ion channels, neurotransmitter receptors, and sonic hedgehog. Protein palmitoyl transferases also use the CoA derivative of the fatty acid as a substrate. Several proteins are modified with both an N-terminal 14 0 and an S-linked 16 0 elsewhere in the protein chain, o-subunits of heterotrimeric G-proteins and endothelial nitric oxide synthase are examples of dually acylated proteins. 

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