Protein functional sites

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

Gene Name Familial Cancer Syndrome Protein Function Sites/Types of Commonly Associated Neoplasms... 

Knowledge of gene sequences for the prediction of function does not yield descriptions of multiple functional sites. Structural descriptors for protein functional sites are essential for deciphering sequence meaning. ... 

Unfortunately, such methods require the exact placement of atoms within protein side chains and are inapplicable to the inexact, low-resolution predicted structures generated by the state-of-the-art ab initio folding and threading algorithms (see Sections IV-VI). These methods are required when the sequence identity of the sequence of interest to solved structures is too low to use comparative modeling. To address this need, Skolnick and Fetrow have recently developed fuzzy, inexact descriptors of protein functional sites [8]. They are applicable to both high-resolution, experimental structures and low-resolution (backbone RMSD 4—6 A from native) structures. These descriptors are a-carbon-based, fuzzy functional forms (FFFs). Initially, they created FFFs for the disulfide oxidoreductase [8,10] and a/p-hydrolase catalytic active sites [11] (an additional 198 have now been bmlt, with comparable results [234]). 

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. 

They also bind small molecules and can be involved in protein-protein interactions. PAS domains in other proteins commonly function either as protein interaction sites or small molecule binding domains. Occasionally,... 

The method utilizing ID NMR is simple and eonvenient. Henee the NMR method diseussed here ean be applied to the systematie investigation of the membrane irug inter-aetions, elosely related to the vital function in biomembranes. It is expected that the application can be extended to the lipid-peptide interaction and protein uptake. We are now applying the method to apolipoprotein binding with lipid bilayers and emulsions. Preferential protein binding sites in membranes can be specified by NMR on the molecular level. 

Fig. 3.4 Three models for prospective function(s) for OBPs during perireceptor delivery of a signal molecule odourant <=> protein <=> receptor site interactions could involve multiple roles. Ligand , OBP , combination(s) buffer and/or carrier and/or transducer from Pelosi, 1994).

Damaj BB, McColl SR, Neote K, et al. Identification of G-protein binding sites of the human interleukin-8 receptors by functional mapping of the intracellular loops. FASEB J 1996 10(12) 1426-1434. 

Polymorphism A common (i.e., at least 1% prevalence of the minor allele in the population) sequence variation observed in an individual at a polymorphic site. Polymorphisms include nucleotide substitutions, insertions, deletions and microsatellites. They may be functional or silent, i.e., they do not result in detectable differences in gene expression or protein function. 

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. 

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. 

---