Protein trans form

Figure 6.9 (a) Peptide units can adopt two different conformations, trans and cis. In the trans-form the C=0 and the N-H groups point in opposite directions whereas in the c/s-form they point in the same direction. For most peptides the trans-form is about 1000 times more stable than the c/s-form. (b) When the second residue in a peptide is proline the trans-form is only about four times more stable than the c/s-form. C/s-proline peptides are found in many proteins. 

FIGURE 8.13 Nonreceptor PTKs. These protein kinases form a large family, and most of them contain SH2 and SH3 domains. Several were originally discovered as transforming genes of a viral genome, hence names such as src or abl, derived from Rous sarcoma virus or Abelson murine leukemia virus, respectively. (Adapted from Hunter, T., Biochem. Soc. Trans., 24(2), 307-327, 1996.)... 

In photoreceptor cells, the rods and cones of the human retina, the retinal is linked to a specific protein termed opsin. The resulting pigment is known as rhodopsin. When a photon of light of the proper wavelength hits a molecule of rhodopsin, two chemical events take place. First, the ll-c -retinal is converted to the all-trans form and, secondly, the all-trani-retinal is released from the rhodopsin ... 

Most peptide bonds in proteins take on the trans conformation (see p. 66). Only bonds with proline residues (-X-Pro-) can be present in both cis and trans forms. 

Vitamin A is essential for proper functioning of the retina, for the integrity of epithelial tissue, for growth and bone development and for reproduction. For vision the active vitamin appears to be retinal as the chromophore of both rods and cones is 11-cis-retinal which, in combination with the protein opsin, forms the photoreceptor rhodopsin. Retinoic acid is the active form associated with growth, differentiation, and transformation. Both all-trans and 9-cis retinoic acid act as a steroid hormone to affect cellular differentiation, especially for morphogenesis, reproduction and for immune responses. At... 

Proline is an exceptional amino acid residue in that the cis-trans equilibrium only slightly favors the trans form in peptidyl-proline bonds. Small proline-containing peptides in solution contain some 5 to 30% of the cis (syn) isomer, as opposed to less than 0.1% of the cis isomers of the other amino acids.14 The cis form is even found in native proteins two of the four prolines in ribonuclease A... 

When this molecule absorbs light, it rapidly isomerizes (changes its structure) to the all-trans form. This specific chemical reaction is the central event in human vision. The molecule is bound within a protein (the combination is called rhodopsin), the isomerization triggers a series of later processes, ultimately leading to an electrical signal which is sent to the brain. 

The biochemistry that mediates photon absorption in the disk membranes and closing of the ionic channels in the plasma membrane is summarized in Fig. 2 and discussed in detail in reviews that provide access to the original literature (Helmreich and Hofmann, 1996 Menon et al, 2001 Hamm 1998, 2001 Bunemann and Hosey, 1999 Krupnick and Benovic, 1998). In the dark (inactive) state, rhodopsin (R) contains a covalently bound 11 -cis retinal chromophore buried within the protein core. In rhodopsin, the chromophore absorbs maximally around 500 nm, and absorption of a photon isomerizes the retinal to the all-trans form within about 200 fs (Peteanu et al, 1993) with a quantum efficiency of 0.67 (Dartnall, 1972). The change in chromophore shape creates strain, and subsequent thermal relaxation of both chromophore... 

RetinalS. The structure and photophysics of rhodopsins are intimately related to the spectroscopic properties of their retiny1-polyene chromophore in its protein-free forms, such as the aldehyde (retinal), the alcohol (retinol or vitamin A), and the corresponding Schiff bases. Since most of the available spectroscopic information refers to retinal isomers (48-55), we shall first center the discussion on the aldehyde derivatives. Three bands, a main one (I) around 380 nm and two weaker transitions at 280 nm and 250 nm (II and III), dominate the spectrum of retinals in the visible and near ultraviolet (Fig. 2). Assignments of these transitions are commonly made in terms of the lowest tt, tt excited states of linear polyenes, the spectroscopic theories of which have been extensively discussed in the past decade (56-60). In terms of the idealized C2h point group of, for example, all-trans butadiene, transitions are expected from the Ta ground state to B , A, and A" excited states... 

Torsion angles, in addition, may be used to designate the conformation of the side chains. These are denoted by x (x X working along the chain away from Ca). The steric interactions within the side chains in the trans form of the peptide bond (u> = 180°) are much more favorable than those in the cis form (w = 0°), where there may also be steric interference with side chains from residues i- -2. If the residue i+1 is proline, however, the cis and trans forms (Figure 12.25) have similar energies. Proline is the only amino acid taking part in a cis peptide that is normally encountered in proteins. 

Cis double bonds produce a kink, or a bend, of about 30 degrees for each double bond into the backbone, and these can flip over to the trans form under high temperatures. Trans double bonds allow the molecule to lie in a straight line however, the human body cannot convert the trans form into nutrients and so prevents the metabolic activities from converting it to the active cis forms. This can lead to a deficiency in essential fatty acids. The more double bonds, and therefore more kinks, the more beneficial it is to human health. By completely changing the physical and chemical properties, the kinks allow essential protein associations to form more easily, thus permitting more saturated fatty acids to disperse and interact with water or blood. 

Tyr from water to an organic solvent, it is not very different from Phe, so we should not be surprised to find it in hydrophobic environments. Gly is an unusual amino acid, with only a hydrogen atom as side chain, and peptide bonds involving Gly residues can take up all sorts of conformations. Pro, which does not have a proton when in a peptide bond, clearly, is hydrophobic, cannot participate in hydrogen bonding, and has the unique capacity among the protein amino acids to be able to form cis-peptide bonds (there is a cis/trans prolyl isomerase to restore the trans form). 

About half of rhodopsln s mass forms seven a-hellces, which are embedded In the lipid bllayer of rod disks. The remaining polypeptide chains extend Into the aqueous environment of the cytoplasm or the disk Interior, linking the helices. Retinal Is bound as a protonated Schiff base to a lysine amino acid residue In the carboxyl terminal helix. The chromophore is held In a pocket that is nearly parallel to the membrane surface. When light strikes rhodopsln, the 11-cis double bond of the protein-bound retinal Isomerlzes to the trans form, which leads to the separation from the protein opsin. To complete the visual cycle, the all-transretlnal slowly Isomerlzes back to the 11-cis Isomer, which recombines with opsin to reform rhodopsln. However, little Is known about how the Isomerization of retinal In rhodopsln triggers the transduction process (72,73) ... 

Fig. 23. (A) The halophilic bacterium H. halobium with patches containing the "purple membrane" (B) Structure of the protein bacteriorhodopsin (left) and the structural formula for the chromophore retinal (right) (C) Covalent binding of retinal with iysine-216 forming a positively-charged Schiff base (D) Illumination of the bacteriorhodopsin retinal and transformation from a trans- to a cis-configuration and releases a proton from the Schiff base to the cell exterior relaxation to ttie trans-form, with uptake of a proton from the cytoplasmic interior. The combination of deprotonation and reprotonation on opposite sides of the membrane constitutes a proton pump. See text for other details. Figures partly adapted from Becker and Deamer (1991) The World of the Cell (2nd ed) Benjamin/Cummings PubI Co. p 215.

Recently Inoue and coworkers also reported ab initio study of shieldings for linear ir-conjugated systems. A photoreceptive protein such as rhodopsin (Rh) or bacte-riorhodopsin (bR) possesses a retinal isomer bound to a lysine residue via the protonated Schiff base linkage. Rh exists in the rod cell of the retina of vertebrate and possesses 11 -cw-retinal (Figure 2), which is isomerized into the all-trans form by the absorption of photons, finally leading to signal transduction. 

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