Conformation and hydrogen bonding of N-formylmethionyl peptides. Parallel beta-sheet in the crystal structure of N-formyl-L-methionyl-L-valine

Crystals of N-formyl-L-methionyl-L-valine (C11H20N2O)4S, M.W. = 276.3) are orthorhombic, space group )2(1)2(1)2(1) with cell constants at 294K of a = 4.851 (1), b = 14.925 (1), c = 19.745 (3) A, V = 1429.8 (1) A3, Z = 4 and observed (Dm) and calculated (Dx) of 1.49 and 1.488 g x cm-3, respectively. The crystal structure was solved using automatic diffractometer data (1260 reflections larger than or equal to 3 sigma) and refined to a final R-value of 0.035. This structure contains a short (2.626 (3) A) intermolecular hydrogen bond between the carboxyl OH and the N-acyl oxygen, a feature common to most N-acylamino acids and N-acylpeptides. The peptide is nearly planar (omega = 174.6 (5)); the values of psi 1, phi 2, psi 1T and psi 2T are, respectively, 131.8 (4) degrees, -139.9 (5) degrees, -39.3 (4) degrees and 142.1 (4) degrees. The methionine side chain is not zig-zag transplanar; the side chain torsion angles are: chi 1(1) = -60.0 (4) degrees, chi 2(1) = 176.0 (4) degrees and chi 3(1) = 71.8 (4) degrees. The two C gamma's for valine have psi 1-values of -64.4 (5) degrees and 173.7 (5) degrees. The formation of the parallel rather than antiparallel beta-sheet structure, the participation of the N-formyl group in the parallel beta-sheet and the use of C-H ... O hydrogen bonds to stabilize the beta-sheet are novel features found in this structure.     

Crystal structure and conformation of glycyl-glycyl-sarcosine

Crystals of the tripeptide, glycyl-glycyl-sarcosine (C7H13N3O4) from aqueous methanol are orthorhombic, space group Pbcn with cell parameters at 294 K of a = 8.279(1), b = 9.229(4), c = 24.447(5)A, V = 1868.0 A3, M.W. = 203.2, and Z = 8. The crystal structure was solved and refined using CAD-4 data (1171 reflections greater than or equal to 3 sigma) to a final R-value of 0.053. The first peptide linkage is trans and planar whereas the second peptide link between Gly and sarcosine is cis and appreciably non-planar (w = 7.4 degrees). The peptide backbone has an extended conformation at the N-terminal part but adopts a polyglycine-II type of conformation at the C-terminal part. The backbone torsion angles are: psi 1 = -173.9, w1 = -177.8, (phi 2, psi 2) = (-178.8, -170.8), w2 = 7.4, (phi 3, psi 3) = (-81.6, 165.6 degrees).     

A spatio-temporal mining approach towards summarizing and analyzing protein folding trajectories

Understanding the protein folding mechanism remains a grand challenge in structural biology. In the past several years, computational theories in molecular dynamics have been employed to shed light on the folding process. Coupled with high computing power and large scale storage, researchers now can computationally simulate the protein folding process in atomistic details at femtosecond temporal resolution. Such simulation often produces a large number of folding trajectories, each consisting of a series of 3D conformations of the protein under study. As a result, effectively managing and analyzing such trajectories is becoming increasingly important.     

Role of sphingosine 1-phosphate in the mitogenesis induced by oxidized low density lipoprotein in smooth muscle cells via activation of sphingomyelinase, ceramidase, and sphingosine kinase.

Oxidized LDL (oxLDL) have been implicated in diverse biological events leading to the development of atherosclerotic lesions. We previously demonstrated that the proliferation of cultured vascular smooth muscle cells (SMC) induced by oxLDL is preceded by an increase in neutral sphingomyelinase activity, sphingomyelin turnover to ceramide, and stimulation of mitogen-activated protein kinases (Augé, N., Escargueil-Blanc, I., Lajoie-Mazenc, I., Suc, I., Andrieu-Abadie, N., Pieraggi, M. T., Chatelut, M., Thiers, J. C., Jaffrézou, J. P., Laurent, G., Levade, T., Nègre-Salvayre, A., and Salvayre, R. (1998) J. Biol. Chem. 273, 12893-12900). Since ceramide can be converted to other bioactive metabolites, such as the well established mitogen sphingosine 1-phosphate (S1P), we investigated whether additional ceramide metabolites are involved in the oxLDL-induced SMC proliferation. We report here that incubation of SMC with oxLDL increased the activities of both acidic and alkaline ceramidases as well as sphingosine kinase, and elevated cellular sphingosine and S1P. Furthermore, the mitogenic effect of oxLDL was inhibited by D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol and N,N-dimethylsphingosine which are inhibitors of ceramidase and sphingosine kinase, respectively. These findings suggest that S1P is a key mediator of the mitogenic effect of oxLDL. In agreement with this conclusion, exogenous addition of sphingosine stimulated the proliferation of cultured SMC, and this effect was abrogated by dimethylsphingosine but not by fumonisin B1, an inhibitor of the acylation of sphingosine to ceramide. Exogenous S1P also promoted SMC proliferation. Altogether, these results strongly suggest that the mitogenic effect of oxLDL in SMC involves the combined activation of sphingomyelinase(s), ceramidase(s), and sphingosine kinase, resulting in the turnover of sphingomyelin to a number of sphingolipid metabolites, of which at least S1P is critical for mitogenesis.     

The expressive movements of the bonnet macaque

A bonnet troop inhabiting Lal Bagh, Bangalore (Hafeezur Rahaman & Parthasarathy, 1967) was exclusively studied for its communicative behavior. The whole system of the bonnet organization is based on composite expressions. Depending on situations, individual signals or a complex of them involving tactile, visual, auditory, and olfactory are passed from one individual to the other.Among tactile signals the most important one is the grooming; among visual the body movement, more particularly the face and jaws; among auditory the groaning and shrieking; among olfactory the sniffing.Analysis of such a study reveals that the bonnet monkeys have a communicative system and an organization of their own, which though principally are the same as in other primates, do entail a few minor differences. These features though primitive from the standards of human consideration, are developed to their full advantage, but still remain at a primitive level. By far, the greatest part of the whole system of communication seems to be devoted to the organization, of the social behavior of the group, to dominance and subordination, the maintenance of peace and cohesion of the group, reproduction and care of the young (Marler, 1965).