Leucine, structure

A likely exit path for the xenon was identified as follows. Different members of our research group placed the exit path in the same location and were able to control extraction of the xenon atom with the tug feature of the steered dynamics system without causing exaggerated perturbations of the structure. The exit path is located between the side chains of leucines 84 and 118 and of valine 87 the flexible side chain of lysine 83 lies just outside the exit and part of the time is an obstacle to a linear extraction (Fig. 1). 

Fig. 9.25 If the leucine side chain interconverts rapidly between too conprmations then the NMR spectrum will he an average of them. With a traditional refinement this leads to a structure that sirmltaiieausly tries to satisfy all restraints and is at the top of the energy barrier between the two minima.

JD Hirst, M Vieth, J Skolmck, CL Brooks III. Predicting leucine zipper structures from sequence. Protein Eng 9 657-662, 1996. 

Figure 3.3 Schematic diagram showing the packing of hydrophobic side chains between the two a helices in a coiled-coil structure. Every seventh residue in both a helices is a leucine, labeled "d." Due to the heptad repeat, the d-residues pack against each other along the coiled-coil. Residues labeled "a" are also usually hydrophobic and participate in forming the hydrophobic core along the coiled-coil.

Figure 3.S Schematic diagram of packing side chains In the hydrophobic core of colled-coll structures according to the "knobs In holes" model. The positions of the side chains along the surface of the cylindrical a helix Is pro-jected onto a plane parallel with the heUcal axis for both a helices of the coiled-coil. (a) Projected positions of side chains in helix 1. (b) Projected positions of side chains in helix 2. (c) Superposition of (a) and (b) using the relative orientation of the helices In the coiled-coil structure. The side-chain positions of the first helix, the "knobs," superimpose between the side-chain positions In the second helix, the "holes." The green shading outlines a d-resldue (leucine) from helix 1 surrounded by four side chains from helix 2, and the brown shading outlines an a-resldue (usually hydrophobic) from helix 1 surrounded by four side chains from helix 2.

Figure 4.10 Consensus amino acid sequence and secondary structure of the leucine-rich motifs of type A and type B. "X" denotes any...

Leucine residues 2, 5, 7, 12, 20, and 24 of the motif are invariant in both type A and type B repeats of the ribonuclease inhibitor. An examination of more than 500 tandem repeats from 68 different proteins has shown that residues 20 and 24 can be other hydrophobic residues, whereas the remaining four leucine residues are present in all repeats. On the basis of the crystal structure of the ribonuclease inhibitor and the important structural role of these leucine residues, it has been possible to construct plausible structural models of several other proteins with leucine-rich motifs, such as the extracellular domains of the thyrotropin and gonadotropin receptors. 

Figure 4.12 Schematic diagram illustrating the role of the conserved leucine residues (green) in the leucine-rich motif in stabilizing the P-loop-(x structural module. In the ribonuclease inhibitor, leucine residues 2, 5, and 7 from the P strand pack against leucine residues 17, 20, and 24 from the a helix as well as leucine residue 12 from the loop to form a hydrophobic core between the P strand and the a helix.

Upha/beta (a/p) structures are the most frequent and most regular of the pro-kein structures. They fall into three classes the first class comprises a central core of usually eight parallel p strands arranged close together like the staves pf a barrel, surrounded by a helices the second class comprises an open twisted parallel or mixed p sheet with a helices on both sides of the p sheet and Ihe third class is formed by leucine-rich motifs in which a large number of parallel p strands form a curved p sheet with all the a helices on the outside bfthis sheet. 

The horseshoe structure is formed by homologous repeats of leucine-rich motifs, each of which forms a p-loop-a unit. The units are linked together such that the p strands form an open curved p sheet, like a horseshoe, with the a helices on the outside of the p sheet and the inside exposed to solvent. The invariant leucine residues of these motifs form the major part of the hydrophobic region between the a helices and the p sheet. 

Kajava, A.V., Vassart, G., Wodak, S.J. Modelling of the three-dimensional structure of proteins with the typical leucine-rich repeats. Structure 3 867-877, 1995. 

Kobe, B., Deisenhofer, J. Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats. Nature 366 751-756, 1993. 

The basic structural unit of these two-sheet p helix structures contains 18 amino acids, three in each p strand and six in each loop. A specific amino acid sequence pattern identifies this unit namely a double repeat of a nine-residue consensus sequence Gly-Gly-X-Gly-X-Asp-X-U-X where X is any amino acid and U is large, hydrophobic and frequently leucine. The first six residues form the loop and the last three form a p strand with the side chain of U involved in the hydrophobic packing of the two p sheets. The loops are stabilized by calcium ions which bind to the Asp residue (Figure S.28). This sequence pattern can be used to search for possible two-sheet p structures in databases of amino acid sequences of proteins of unknown structure. 

Figure 10.18 Side-chain interactions in the leucine zipper structure, (a) The hydrophobic side chains in spikes a and d (see Figure 10.17) form a hydrophobic core between the two coiled a helices, (b) Charged side chains in spikes and g can promote dimer formation by forming complementary charge interactions between the two a helices.

The coiled-coil structure of the leucine zipper motif is not the only way that homodimers and heterodimers of transcription factors are formed. As we saw in Chapter 3 when discussing the RNA-binding protein ROP, the formation of a four-helix bundle structure is also a way to achieve dimerization, and the helix-loop-helix (HLH) family of transcription factors dimerize in this manner. In these proteins, the helix-loop-helix region is preceded by a sequence of basic amino acids that provide the DNA-binding site (Figure 10.23), and... 

Helix-loop-helix (b/HLH) transcription factors are either heterodimers or homodimers with basic a-helical DNA-binding regions that lie across the major groove, rather than along it, and these helices extend into the four-helix bundle that forms the dimerization region. A modification of the b/HLH structure is seen in some transcription factors (b/HLH/zip) in which the four-helix bundle extends into a classic leucine zipper. 

Ellenberger, T.E., et al. The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted a helices crystal structure of the protein-DNA complex. Cell 71 1223-1237, 1992. 

O Shea, E.K., et al. X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. Science 254 539-544, 1991. 

From a map at low resolution (5 A or higher) one can obtain the shape of the molecule and sometimes identify a-helical regions as rods of electron density. At medium resolution (around 3 A) it is usually possible to trace the path of the polypeptide chain and to fit a known amino acid sequence into the map. At this resolution it should be possible to distinguish the density of an alanine side chain from that of a leucine, whereas at 4 A resolution there is little side chain detail. Gross features of functionally important aspects of a structure usually can be deduced at 3 A resolution, including the identification of active-site residues. At 2 A resolution details are sufficiently well resolved in the map to decide between a leucine and an isoleucine side chain, and at 1 A resolution one sees atoms as discrete balls of density. However, the structures of only a few small proteins have been determined to such high resolution. 

The nonpolar amino acids (Figure 4.3a) include all those with alkyl chain R groups (alanine, valine, leucine, and isoleucine), as well as proline (with its unusual cyclic structure), methionine (one of the two sulfur-containing amino acids), and two aromatic amino acids, phenylalanine and tryptophan. Tryptophan is sometimes considered a borderline member of this group because it can interact favorably with water via the N-H moiety of the indole ring. Proline, strictly speaking, is not an amino acid but rather an a-imino acid. 

Transfer RNA (tRNA) serves as a carrier of amino acid residues for protein synthesis. Transfer RNA molecules also fold into a characteristic secondary structure (marginal figure). The amino acid is attached as an aminoacyl ester to the 3 -terminus of the tRNA. Aminoacyl-tRNAs are the substrates for protein biosynthesis. The tRNAs are the smallest RNAs (size range—23 to 30 kD) and contain 73 to 94 residues, a substantial number of which are methylated or otherwise unusually modified. Transfer RNA derives its name from its role as the carrier of amino acids during the process of protein synthesis (see Chapters 32 and 33). Each of the 20 amino acids of proteins has at least one unique tRNA species dedicated to chauffeuring its delivery to ribosomes for insertion into growing polypeptide chains, and some amino acids are served by several tRNAs. For example, five different tRNAs act in the transfer of leucine into... 

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