Protein SMART

Cell or protein smart delivery systems are desirable as they allow precise application to a local site. For optimal design the material should be a solution at room temperature and gel within the body at physiological temperature and... 

Heredia KL, Bontempo D, Ly T, Byers JT, Halstenberg S, Maynard HD. In situ preparation of protein smart polymer conjugates with retention of bioactivity. J Am Chem Soc 2005 127 16955-16960. 

Similar residues in the cores of protein structures especially hydrophobic residues at the same positions, are responsible for common folds of homologous proteins. Certain sequence profiles of conserved residue successions have been identified which give rise to a common fold of protein domains. They are organized in the smart database (simple modular architecture research tool) http //smait.embl-heidelberg.de. 

Uittenbogaard, A, Everson, WV, Matveev, SV, and Smart, EJ, 2002. Cholesteryl ester is transported from caveolae to internal membranes as part of a caveolin-annexin II lipid-protein complex. J Biol Chem 277,4925—4-931. 

Zhou, R. Berne, B.J., Smart walking A new method for Boltzmann sampling of protein conformations, J. Chem. Phys. 1997,107, 9185... 

Ponting CP, Schultz J, Milpetz F, Bork P. SMART identification and annotation of domains from signalling and extracellular protein sequences. Nucleic Acids Res 1999 27[l] 229-232. 

Many kinds of nonbiodegradable vinyl-type hydrophilic polymers were also used in combination with aliphatic polyesters to prepare amphiphilic block copolymers. Two typical examples of the vinyl-polymers used are poly(/V-isopropylacrylamide) (PNIPAAm) [149-152] and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) [153]. PNIPAAm is well known as a temperature-responsive polymer and has been used in biomedicine to provide smart materials. Temperature-responsive nanoparticles or polymer micelles could be prepared using PNIPAAm-6-PLA block copolymers [149-152]. PMPC is also a well-known biocompatible polymer that suppresses protein adsorption and platelet adhesion, and has been used as the hydrophilic outer shell of polymer micelles consisting of a block copolymer of PMPC -co-PLA [153]. Many other vinyl-type polymers used for PLA-based amphiphilic block copolymers were also introduced in a recent review [16]. 

Smart, T. G. Regulation of excitatory and inhibitory neuro-transmitter-gated ion channels by protein phosphorylation. Curr. Opin. Neurobiol. 7 358-367,1997. 

Moser GJ, Smart RC. 1989. Hepatic tumor-promoting chlorinated hydrocarbon stimulate protein kinase C activity. Carcinogenesis 10(5) 851-856. 

It can be difficult if not impossible to find the domain structure of a protein of interest from the primary literature. The sequence may contain many common domains, but these are usually not apparent from searches of literature. Articles defining new domains may include the protein, but only in an alignment figure, which are not searchable. Perhaps, with the advent of online access to articles, the full text including figures may become searchable. Fortunately there have been several attempts to make this hidden information available in away that can be easily searched. These resources, called domain family databases, are exemplified by Prosite, Pfam, Prints, and SMART. These databases gather information from the literature about common domains and make it searchable in a variety of ways. They usually allow a researcher to look at the domain organization of proteins in the sequence database that have been precalculated and also provide a way to search new sequences... 

In the detection of repeats using SMART an algorithm is used that derives similarity thresholds that are dependent on the number of repeats already found in a protein sequence (Andrade et al., 1999b). These thresholds are based on the assumption that suboptimal local alignment scores of a profile/HMM against a random sequence database are well described by an extreme value distribution (EVD). The result of this protocol is that acceptance thresholds for suboptimal alignments are lowered below the optimal scores of nonhomologous sequences. 

Multiple alignments of repeats are constructed in an iterative manner. The initial alignment is based on definitions from determined protein structures or else from the literature. In the initial database search step, a profile constructed from the multiple alignment is compared with a sequence database. Top scoring sequences are considered using complementary approaches such as PSI-BLAST and FASTA to provide the two thresholds minimum E value and minimum number of repeats per protein required. After one or two iterations, the final alignment and the thresholds are stored in the SMART database to allow the detection of repeats in any sequence. 

A variety of domain or motif families occur only as extensions to other domains. The Bruton s tyrosine kinase motif (BTK), for example, is found only at the C terminus of PH domains. Similarly, a C-terminal extension (the S TK X domain) to some subfamilies of serine/threonine kinases (S TK) is not found in isolation. Cases where only the extension, and not the preceding domain, is found are strong evidence that the proteins are wrongly assembled from genomic sequence or else represent partial cDNA sequences (Fig. 9, see Color insert). Indeed, all five proteins annotated in SMART as containing a S TK X domain with no catalytic domain are noted to be fragments in their corresponding sequence database entries. 

E. J. Smart, D. C. Foster, Y. S. Ying, B. A. Kamen, and R. G. Anderson. Protein kinase C activators inhibit receptor-mediated potocytosis by preventing internalization of caveolae. J. Cell Biol. 124 307-313 (1994). 

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