Aromaticity three dimensional structures

This is nicely illustrated by members of the chymotrypsin superfamily the enzymes chymotrypsin, trypsin, and elastase have very similar three-dimensional structures but different specificity. They preferentially cleave adjacent to bulky aromatic side chains, positively charged side chains, and small uncharged side chains, respectively. Three residues, numbers 189, 216, and 226, are responsible for these preferences (Figure 11.11). Residues 216... 

Fig. 11.2. Schematic representation of the primary structure of secreted AChE B of N. brasiliensis in comparison with that of Torpedo californica, for which the three-dimensional structure has been resolved. The residues in the catalytic triad (Ser-His-Glu) are depicted with an asterisk, and the position of cysteine residues and the predicted intramolecular disulphide bonding pattern common to cholinesterases is indicated. An insertion of 17 amino acids relative to the Torpedo sequence, which would predict a novel loop at the molecular surface, is marked with a black box. The 14 aromatic residues lining the active-site gorge of the Torpedo enzyme are illustrated. Identical residues in the nematode enzyme are indicated in plain text, conservative substitutions are boxed, and non-conservative substitutions are circled. The amino acid sequence of AChE C is 90% identical to AChE B, and differs only in the features illustrated in that Thr-70 is substituted by Ser.

Aromaticity Evaluations of Three-dimensional Structures Nucleus-Independent Chemical Shift (NICS)... 

Fig. 3.2-1. Electron-rich (A, B) and electron-precise (C) planar aromatics as well as three dimensional structures D—L as a result of less skeletal electrons (SE). Lines in electron-deficient corn-pounds indicate connectivities not 2c2e bonds.

Several NMR studies have been carried out in order to reveal the three-dimensional structure of CBMs and to understand the mechanism by which CBMs from thermophilic organisms bind to their polysaccharide ligands (CBM22, CBM4, and CBM4-2 ). It has been found that CBMs are composed mainly of jS-strand and contain a planar hydrophobic platform comprising aromatic residues that bind to the surface of the polysaccharide. 

Theoretical studies indicate that the allotrope, Qg, is a planar cyclic structure and therefore has one planar cyclic array of 18 electrons of the above type. It also has a second cyclic 18-electron array in the a framework, albeit the orbitals overlap in fashion [254]. The allotrope, [255], has a cyclic polyaromatic three-dimensional structure which has also been argued to be aromatic [256]. 

The three-dimensional structures, or part of it, are also known for Desulfovibrio vulgaris and Anacystis nidulans flavodoxins. These results, including those obtained on C.MP., were recently summarized by Adman . Hence, these results will be discussed only briefly. The x-ray structures show that the isoalloxazine ring is embedded in a hydrophobic pocket of the apoprotein, i.e. flanked by at least one aromatic amino acid residue. During the redox transitions, especially from the oxidized to the semiquinone state, small conformational changes occur and contacts with the isoalloxazine ring are formed or broken. These conformational transitions form probably a kinetic barrier so that the semiquinone state is trapped by the apoprotein and, therefore, rather stable towards oxidation by molecular oxygen. 

Bovine pancreatic chymotrypsin (Mr 25,191) is a protease, an enzyme that catalyzes the hydrolytic cleavage of peptide bonds. This protease is specific for peptide bonds adjacent to aromatic amino acid residues (Trp, Phe, Tyr). The three-dimensional structure of chymotrypsin is shown in Figure 6-18, with functional groups in the active site emphasized. The reaction catalyzed by this enzyme illustrates the principle of transition-state stabilization and also provides a classic example of general acid-base catalysis and covalent catalysis. 

Most ribosomal proteins are rich in lysine and arginine and, therefore, carry a substantial net positive charge. Proteins S20, L7/12, and L10 have over 20% alanine, while L29 is almost as rich in leucine. Proteins S10, S13, L7/L12, L27, L29, and L30 are surprisingly low (<2 mol %) in aromatic amino acids. Proteins S5, S18, and L7 have acetylated N termini while Lll, L3, L7/12, Lll, L16, and L33 contain methylated amino acids. Lll contains nine methyl groups.22 Protein S6 is the major phosphoprotein of eukaryotic ribosomes.103104 Most ribosomal proteins have no known enzymatic activity. Although often difficult to crystallize, high-resolution three-dimensional structures are known for many free ribosomal proteins.24 Most of them have shapes resembling those previously found... 

Cholesterol is the most common steroid of mammalian membranes. It is formed biologically from lanosterol, as shown. Ergosterol is the most common steroid of fungal membranes. It differs from cholesterol by the presence of two additional double bonds that affect its three dimensional structure. Also shown are three so-called steroid hormones, andros-terone, estradiol, and testosterone. Note the presence of an aromatic A-ring in estradiol. 

Fig. 17. Model of the three-dimensional structure of carp parvalbumin showing the a-carbon backbone and a group of phenylalanine side chains, which form an enthalpically favorable set of aromatic-aromatic interactions and, to a large extent, define the core structure of this protein.

PTPS (6-Pyruvoyl Tetmhydropterin Synthase). 6-Pyruvoyl tetrahy-dropterin synthase catalyzes formation of tetrahydrobiopterin biosynthesis. Tetrahydrobiopterin is a cofactor for several important enzymes, such as aromatic amino acid hydroxylases and nitric oxide synthase (57). H. pylori protein HPAG1 0913 shares homology with members of the protein domain family PTPS. H. pylori protein shares poor sequence identity of 14% with the PTPS profile at an E-value of 10 10 and covers about 95% of the length of the profile. Fold recognition results also confirm the relationship between H. pylori protein and the PTPS protein domain family. A fold recognition algorithm ensures fitness of the H. pylori protein sequence on the three-dimensional structure of PTPS from... 

Many applications have been reported in the field of biomolecular NMR spectroscopy which use RDCs for the refinement of three-dimensional structures. The approach is quite powerful and can also be applied to smaller molecules whenever the conformation of a molecule is important, as for example in the case of rational drug design. Traditionally, NMR in liquid crystals is applied on a multitude of small organic compounds to obtain their fully characterized structure. Most examples are measured on all kinds of aromatic systems as reported in refs. 204—212 other recent examples deal with substituted alkanes, aldehydes216,217 or bridged systems like norbomadiene.218 In general, these very detailed studies can be applied to molecules with up to 12 protons. 

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