Protein targets, number

Entry Small molecule Structure Protein target Number of citations... 

As the availability of crystal structures increased in the early 1990s, a number of experimental and computational methods were developed to use the structure of the protein target as a route to discover novel hit compounds. The methods include de novo design, virtual screening, and fragment-based discovery. These developments are covered in more detail in the later chapters of this book, but their main features can be summarized as follows. 

An important question that needs to be addressed in any screening study is the determination of whether or not the ligand is non-covalently bound to the active site of the target protein. A number of simple GPC spin column ESI-MS screening methods have been developed to answer this question. These methods include the use of mutated proteins where the active site has been modified, GPC spin column/ESI-MS coupled with NMR (GPC spin column/MS/NMR) and displacement of known binders. Titration experiments with molar excesses of ligand to protein (described below in Section 2.3.3.2.4) can also be used to determine whether single or multiple binding sites are available in the protein. 

Beau has applied the DCC concept to a number of carbohydrate systems [13-16]. Carbohydrate-binding proteins often exhibit weak ligand interactions with millimolar dissociation constants, a quite different scenario to the enzyme-small molecule DCLs discussed thus far. The protein target initially chosen for study was hen egg-white lysozyme (HEWL), a glycosidase known to bind A-acetyl-o-glucosamine (d-G1cNAc) with... 

Postulated relationship between species diversity and number of potential protein targets Individual species... 

Nuclear importation is mediated by a number of proteins that cycle between the cytosol and the nucleus (Fig. 27-37), including importin a and J8 and a small GTPase known as Ran. A heterodimer of importin a and J8 functions as a soluble receptor for proteins targeted to the nucleus, with the a subunit binding NLS-bearing... 

Initiation (Figs. 29-10 and 29-11), elongation (Fig. 29-12), and termination are three distinct steps in the synthesis of a protein. A variety of specialized proteins are required for each stage of synthesis. Their sequential interaction with ribosomes can be viewed as a means of ensuring an orderly sequence of steps in the synthesis cycle. The rate of protein formation will depend upon the concentrations of amino acids, tRNAs, protein factors, numbers of ribosomes, and kinetic constants. The formation of specific proteins can also be inhibited by translational repressors, proteins that compete with ribosomes for binding to target mRNAs.287... 

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