Functional site

Determination of DNA Sequence Information. Almost all DNA sequence is determined by enzymatic methods (12) which exploit the properties of the enzyme DNA polymerase. Whereas a chemical method for DNA sequencing exists, its use has been supplanted for the most part in the initial deterrnination of a sequence. Chemical or Maxam-Gilbett sequencing (13) is mote often used for mapping functional sites on DNA fragments of known sequence. 

Nonrepetitive but well-defined structures of this type form many important features of enzyme active sites. In some cases, a particular arrangement of coil structure providing a specific type of functional site recurs in several functionally related proteins. The peptide loop that binds iron-sulfur clusters in both ferredoxin and high potential iron protein is one example. Another is the central loop portion of the E—F hand structure that binds a calcium ion in several calcium-binding proteins, including calmodulin, carp parvalbumin, troponin C, and the intestinal calcium-binding protein. This loop, shown in Figure 6.26, connects two short a-helices. The calcium ion nestles into the pocket formed by this structure. 

Isoform Mass (kDa) Gene name Amino acids Domains Domain location (approx.) Domain function Site of major expression Chromosome location... 

Spatial relationships between functional sites in the sarcoplasmic reticulum Ca -ATPase... 

Intramolecular distances between functional sites of the Ca transfer... 

For more efficient utilization of MOFs sorbents, several hybrid systems based on MOFs with other solid sorbents have been investigated in the literature. The objective of having hybrid materials is to utilize the synergism between the two sorbents and therefore ultimately improve the overall performance in C02 separation. Moreover, sorbents such as activated carbons, graphenes, and CNTs provide the added feature of high surface area and easily functionalized sites which contribute to the tuning of the final properties of the composite... 

From 13 completed amino-acid sequences and 54 partial sequences (>40 residues) of plastocyanins from higher plants it appears that sixty residues are invariant and 7 are conservatively substituted 02,7). With three algal plastocyanins included there are 39 invariant or conservatively substituted groups. It is believed that the same structural features apply to the whole family, and that highly conserved residues are an indication of functional sites on the protein surface. The upper hydrophobic and right-hand-side surfaces are believed to be particularly relevant in this context, the latter including four consecutive... 

Figure 9. Behavior expected if there are two separate functional sites on the protein for electron transfer. One site (Site 1) is blocked directly by redox inactive 3 < 4 < 5 complexes, the other (Site 2) is not blocked.

The effect is of similar magnitude to that observed for blocking by the 3+ redox inactive Co (1 3)53+ ( 30% decrease). Use of Cr(III) modified protein has no effect on the reaction with Fe(CN)53- as oxidant. These observations (21) support the belief that positive and negative redox partners utilize different functional sites on the protein for electron transfer. 

A large number of other host compounds have been designed to incorporate functional sites which are suitably placed for interaction with the binding sites of a guest. Molecular models suggested (Newcomb, Timko, Walba Cram, 1977) that the somewhat more rigid ring in the... 

Prosite (http //www.expasy.org/prosite), database of protein domains, families, and functional sites. 

InterPro (http //www.ebi.ac.uk/interpro), database of protein families, domains, and functional sites allows prediction of the function or structure of a new protein on the basis of its sequence homology to sequences of known proteins. 

In order to avoid tedious procedures required to prepare packed CEC columns, some groups are studying the use of empty capillaries. Since solute-stationary phase interactions are key to the CEC process, appropriate moieties must be bound to the capillary wall. However, the wall surface available for reaction is severely limited. For example, a 100 pm i.d. capillary only has a surface area of 3xl0 4m2 per meter of length, with a density of functional sites of approximately 3.1 xlO18 sites/m2, which equals 0.5 pmol sites/m2. Moreover, surface modification cannot involve all of the accessible silanol groups, since some must remain to support the EOF. As a result, the use of bare capillaries in CEC has been less successful. 

The majority of prosite documentation refers to motifs rather than profiles. The motifs are less sensitive than profiles and do not provide statistical scores. The motifs correspond to active sites and other important functional sites in proteins. The motifs are expressed as regular expressions that can be used to detect matching proteins in the database. An example of a motif from Prosite would be the /V-glycosylation motif,... 

Many bioinformatics programs exist that provide information to allow determining if the candidate SNP may interfere with a potential functional site (see Table 12.1). Polymorphism Mining and Annotation Programs (PolyMAPr) (21) provides this information in a particularly efficient way once a file containing the annotated gene sequence has been entered. PolyMAPr wiU then map all SNP sequences taken... 

Kalinina OV, Gelfand MS, RusseU RB (2009) Combining specificity determining and conserved residues improves functional site prediction. Bioinformatics. doi 10.1186/1471-... 

Campbell SJ, Gold ND, Jackson RM, et al. ligand binding functional site location, similarity and docking. Curr Opin Struct Biol 2003 13 389-95. 

The ligand binding or catalytic sites are the most relevant parts of a protein domain for the development of small molecules as modulators of protein function. There is evidence that proteins with conserved folds often also have their functional sites on the same topological location. In some cases a remarkable conservatism in functional sites can be observed. This is true for the example described later in this review on similarity of Cdc25A phosphatase, acetylcholinesterase (AChE) and 1 Ifl-hydroxysteroid dehydrogenases (1 l HSD) (Fig. 9). Nevertheless, it should be stressed that the correlation patterns of amino acid sequence, protein fold and protein function remain a matter of debate. Moreover, a vast number of specific functions can be carried out by the limited number of protein domains due to the high amino acid diversity of proteins with similar folds. " ... 

Chain ends are often functionalized with groups that can react with specific sites on another molecule. These functionalized sites are referred to as molecular alligator clips. The chain shown in structure 19.13 has two such functionalized groups or alligator clips, one on each end. These molecular alligator clips are normally designed to attach or anchor to a metal surface. Thus, this molecule is a candidate to connect two electrodes, acting as a molecular wire. 

Jambon M, Andrieu O, Combet C et al (2005) The SuMo server 3D search for protein functional sites. Bioinformatics 21 3929-3930... 

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