1. [Crystalline structure of L-leucyl-L-leucyl-L-tyrosine chlorhydrate]
J Delettré, J Berthou, A Lifchitz, P Jollès Acta Crystallogr C. 1988 May 15;44 ( Pt 5):905-7. doi: 10.1107/s0108270188000940.
C21H34N3O5+.Cl-, Mr = 444.0, orthorhombic, P2(1)2(1)2(1), a = 26.074 (5), b = 17.591 (4), c = 5.224 (2) A, V = 2396.1 (10) A3, Z = 4, Cu K alpha, lambda = 1.5418 A, mu = 1.71 mm-1, F(000) = 952, D chi = 1.231 Mg m-3, room temperature, final R = 0.080 and wR = 0.070 for 2439 reflections [(sin theta)/lambda greater than 0.03 A-1]. The peptide groups are planar; torsion angles (-101 and -88 degrees) indicate a roughly helical structure. The peptide bonds have a trans conformation. The crystal structure is stabilized by a network of hydrogen bonds.
2. Ceramide selectively decreases tau levels in differentiated PC12 cells through modulation of calpain I
H Xie, G V Johnson J Neurochem. 1997 Sep;69(3):1020-30. doi: 10.1046/j.1471-4159.1997.69031020.x.
Ceramide has been recently proposed to be a signal mediator in several important physiological processes including apoptosis, cellular growth, and differentiation. Because the microtubule-associated protein tau plays an important role in the establishment and maintenance of neuronal morphology, the effects of ceramide on tau were examined. Treatment of differentiated PC12 cells with the cell-permeable ceramide derivative N-acetylsphingosine (C2) resulted in a significant reduction in tau levels. Significant decreases in tau levels were also observed when the cells were treated with another ceramide derivative, N-hexanoylsphingosine (C6). In addition, C2 treatment increased the levels of a calpain-derived spectrin breakdown product but did not alter the levels of two cytoskeletal proteins, alpha-actin and alpha-tubulin. Because both tau and spectrin are proteolyzed in vitro by the calcium-activated cysteine protease calpain, the effects of ceramide analogues on the activity of this protease were examined. Treatment of PC12 cells with C2 enhanced calcium-stimulated proteolytic activity significantly, as revealed by monitoring the hydrolysis of the membrane-permeable calpain-selective fluorescence probe N-succinyl-L-leucyl-L-leucyl-L-valyl-L-tyrosine-7-amido-4-methylcoumarin . This activity increase was not due to a direct effect of C2 on calpains, because C2 did not alter the activities of purified calpain I or II. In addition, C2 treatment of PC12 cells resulted in a significant increase in the levels of calpain I and, to a lesser extent, the levels of calpastatin (an endogenous calpain inhibitor protein), whereas the levels of calpain II were not changed. Moreover, treatment of the cells with the synthetic calpain-specific inhibitor N-carbobenzoxy-L-leucyl-L-leucyl-L-tyrosine diazomethyl ketone blocked the C2-induced decreases in tau levels. These results indicate that tau levels are regulated in response to a physiological factor and, thus, have implications for ceramide-mediated changes in normal and pathological neuronal processes.
3. Glycyl-L-leucyl-L-tyrosine dihydrate 2-propanol solvate
B Dalhus, C H Görbitz Acta Crystallogr C. 1996 Aug 15;52 ( Pt 8):2087-90. doi: 10.1107/s0108270196002041.
The asymmetric unit (C17H25N3O5.C3H8O.2H2O) consists of two crystallographically independent peptide molecules, A and B, with different conformations, chi 1(2) being trans and gauche- for the Leu residues in molecules A and B, respectively. The backbone conformation of both peptide molecules resembles that of the beta-pleated sheet arrangement found in proteins. Comparison with two other structures containing the tripeptide Gly-L-Leu-L-Tyr reveals almost identical molecular conformations, and in one instance also a common packing pattern.
