Proteins structural diversity

Proteins are the indispensable agents of biological function, and amino acids are the building blocks of proteins. The stunning diversity of the thousands of proteins found in nature arises from the intrinsic properties of only 20 commonly occurring amino acids. These features include (1) the capacity to polymerize, (2) novel acid-base properties, (3) varied structure and chemical functionality in the amino acid side chains, and (4) chirality. This chapter describes each of these properties, laying a foundation for discussions of protein structure (Chapters 5 and 6), enzyme function (Chapters 14-16), and many other subjects in later chapters. 

Applications of neural networks are becoming more diverse in chemistry [31-40]. Some typical applications include predicting chemical reactivity, acid strength in oxides, protein structure determination, quantitative structure property relationship (QSPR), fluid property relationships, classification of molecular spectra, group contribution, spectroscopy analysis, etc. The results reported in these areas are very encouraging and are demonstrative of the wide spectrum of applications and interest in this area. 

Proteins derive their powerful and diverse capacity for molecular recognition and catalysis from their ability to fold into defined secondary and tertiary structures and display specific functional groups at precise locations in space. Functional protein domains are typically 50-200 residues in length and utilize a specific sequence of side chains to encode folded structures that have a compact hydrophobic core and a hydrophilic surface. Mimicry of protein structure and function by non-natural ohgomers such as peptoids wiU not only require the synthesis of >50mers with a variety of side chains, but wiU also require these non-natural sequences to adopt, in water, tertiary structures that are rich in secondary structure. 

Figure 11.5 Amino acid building blocks are incorporated into daptomycin backbone successively by NRPS subunits DptA, DptBC and DptD (a). Structural diversity of daptomycin peptide core can be obtained by genetic modifications of dpt gene cluster (b). C, condensation domain A, adenylation domain PCP, peptidyl carrier protein E, epimerase TE, thioesterase domain... 

The term "structural genomics" is used to describe how the primary sequence of amino acids in a protein relates to the function of that protein. Currently, the core of structural genomics is protein structure determination, primarily by X-ray crystallography, and the design of computer programs to predict protein fold structures for new proteins based on their amino acid sequences and structural principles derived from those proteins whose 3-dimensional structures have been determined. Plant natural product pathways are a unique source of information for the structural biologist in view of the almost endless catalytic diversity encountered in the various pathway enzymes, but based on a finite number of reaction types. Plants are combinatorial chemists par excellence, and understanding the principles that relate enzyme structure to function will open up unlimited possibilities for the... 

Protein structures are so diverse that it is sometimes difficult to assign them unambiguously to particular structural classes. Such borderline cases are, in fact, useful in that they mandate precise definition of the structural classes. In the present context, several proteins have been called //-helical although, in a strict sense, they do not fit the definitions of //-helices or //-solenoids. For example, Perutz et al. (2002) proposed a water-filled nanotube model for amyloid fibrils formed as polymers of the Asp2Glni5Lys2 peptide. This model has been called //-helical (Kishimoto et al., 2004 Merlino et al., 2006), but it differs from known //-helices in that (i) it has circular coils formed by uniform deformation of the peptide //-conformation with no turns or linear //-strands, as are usually observed in //-solenoids and (ii) it envisages a tubular structure with a water-filled axial lumen instead of the water-excluding core with tightly packed side chains that is characteristic of //-solenoids. 

Kajava, A. V. (1998). Structural diversity of leucine-rich repeat proteins. J. Mol. Biol. 277,... 

Amyloid fibrils form from a variety of native proteins with diverse sequences and folds. The classic method for the structural analysis of amyloid has been X-ray fiber diffraction amyloid fibrils exhibit a characteristic diffraction signature, called the cross-/) pattern. This cross-/ pattern suggested a repeating structure in which /1-sheets run parallel to the fiber axis with their constituent /1-strands perpendicular to that direction (Sunde and Blake, 1997). This diffraction signature pointed to an underlying common core molecular structure for the amyloid fibril that could accommodate diverse sequences and folds. A number of groups have proposed amyloid folds that are consistent with the experimental data and these can be linked to repeating /1-structured units. 

All polyketides use the same general mechanism for chain elongation. Acetyl coenzyme A provides acetate (C2) units, which are condensed by a ketosynthase (KS). This in turn catalyzes condensation of the growing chain onto an acyl carrier protein (ACP), as generalized in Fig. 1.4. Enzymes such as ketoreductase (KR), enoyl reductase (ER), and dehydratase (DH) establish the oxidation state of caibon during translation, imparting structural diversity. Successive translation of each module leads to a chain of the required length that is eventually passed to thioeste-rase (TE), which releases the chain as a free acid or lactone. 

The greater number of folds in larger proteomes is intuitively obvious simply because the functioning of more complex organisms is expected to require a greater structural diversity of proteins. From a different perspective, the increase of diversity follows from a stochastic model, which describes a proteome as a finite sample from an infinite pool of proteins with a particular distribution of fold fractions ( a bag of proteins ). A previous random simulation analysis suggested that the stochastic model significantly (about twofold) underestimates the number of different folds in the proteomes (Wolf et al., 1999). In other words, the structural diversity of real proteomes does not seem to follow... 

F-box proteins serve as the substrate-targeting subunit of the SCF ubiquitin E3 ligase [5]. They are structurally diverse but they all contain a relatively conserved signature motif of about 45-50 amino acids [5]. This motif, the F-box, was initially... 

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