Templates, structural

The aim of the fust dimension breadth is to reveal sequence-function relationships by comparing protein sequences by sequence similarity. Simple bioinformatic algorithms can be used to compare a pair of related proteins or for sequence similarity searches e.g., BLAST (Basic Local Alignment Search Tool). Improved algorithms allow multiple alignments of larger number of proteins and extraction of consensus sequence pattern and sequence profiles or structural templates, which can be related to some functions, see e.g., under http //www. expasy.ch/tools/ similarity. 

In the protein structure database PDB ( http //www. rcsb.org/pdb), by X-ray crystallography and NMR spectroscopy, experimentally solved 3D-protein structures are available to the public. Homology model building for a query sequence uses protein portions of known 3D-stmctures as structural templates for proteins with high sequence similarity. 

If the sequence of a protein has more than 90% identity to a protein with known experimental 3D-stmcture, then it is an optimal case to build a homologous structural model based on that structural template. The margins of error for the model and for the experimental method are in similar ranges. The different amino acids have to be mutated virtually. The conformations of the new side chains can be derived either from residues of structurally characterized amino acids in a similar spatial environment or from side chain rotamer libraries for each amino acid type which are stored for different structural environments like beta-strands or alpha-helices. 

The margin of error of a final structural model depends on the sequence or fold similarity to the starting structural template. 

Based on the three-dimensional structure of CHS, we proposed that the initiation/elongation/cyclization cavity serves as a structural template that selectively stabilizes a particular folded conformation of the linear tetraketide, allowing the Claisen condensation to proceed from C6 to Cl of the reaction intermediate.14 In contrast, CTAL formation can occur either in solution or alternatively while sequestered in the enzyme active site. In either case, enolization of the C5 ketone followed by nucleophilic attack on the Cl ketone with either a hydroxyl group (in solution) or the cysteine thiolate (enzyme bound) as the leaving group results in CTAL. Similar lactones are commonly formed as by-products of in vitro reactions in other PKS systems.36 38... 

It yields generalizable structural templates for cognate families of these proteins, and identifies functionally important details about various subtypes (3,5,7). 

The idea of ESSENS (Kleywegt and Jones, 1997) is to recognize secondary structural templates around each point in the map by an exhaustive search. This... 

The rational method features the functional approach and structural template approach. 

Figure 41. The SEM micrograph images of an Er 1 Ti()2 inverse-opal structure templated using a colloidal crystal of 466-nm polystyrene beads by filling the interstitial volumes with colloidal 50-nm diameter Lr 1 Ti()2 nanocrystals followed by calcination to remove the poylystyrene. (a) Low magnification. (b) High magnification. [Adapted from (187).]...

TABLE 6.12 Production spectra of (M + H)+ ions of buspirone metabolites and their structural interpretation based on buspirone as a structural template... 

Figure 6.42 Product ion spectrum of CPT-11, the structural template for the identification of metabolite structures. (Reprinted with permission from Lokiec et al., 1996. Copyright 1996 American Association for Cancer Research.)...

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