Binding Sites in Proteins

The major metal-binding amino acid side chains in proteins (Gurd and Wilcox, 1956 see Voet and Voet, 1990) (Table II) are carboxyl (aspartic acid and glutamic acid), imidazole (histidine), indole (tryptophan), thiol (cysteine), thioether (methionine), hydroxyl (serine, threonine, and tyrosine), and possibly amide groups (asparagine and glutamine, although 

Group Abbreviation Formula Metal-binding atom 

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Poorly soluble brickdust compounds are not preferentially selected for by HTS as is the case with greaseballs. However, brickdust compounds are extremely common in certain popular current era targets, e.g. the ATP competitive hinge region binding site in protein kinase inhibitors. 

Similarly, photolabels, such as 4-azidobenzoylglycine can be attached to peptides and used to detect binding sites in proteins.137... 

Alberts, I. L., Nadassy, K., and Wodak, S. J. (1998) Analysis of zinc binding sites in protein crystal structures. Protein. Sci. 7,1700-1716. 

Unlike the other alkaline earth and transition metal ions, essentially on account of its small ionic radius and consequent high electron density, Mg2+ tends to bind the smaller water molecules rather than bulkier ligands in the inner coordination sphere. Many Mg2+-binding sites in proteins have only 3, 4 or even less direct binding contacts to the protein, leaving several sites in the inner coordination sphere occupied by water, or in the phosphoryl transferases, by nucleoside di- or triphosphates. 

Sotriffer C, Klebe G. 2002. Identification and mapping of smaU-molecule binding sites in proteins computational tools for structure-based drug design. Farmaco 57(3) 243-251. 

Other Proteins The ouabain-binding site on (Na /K -adenosine-5 -triphosphatase, 46, 523 penicillin isocyanates for /3-lactamase, 46, 531 active site-directed addition of a small group to an enzyme the ethylation of ludferin, 46, 537 mandelate racemase, 46, 541 d imethylpyrazole carboxamidine and related derivatives, 46, 548 labeling of catechol O-methyltransferase with N-haloace-tyl derivatives, 46, 554 affinity labeling of binding sites in proteins by sensitized photooxidation, 46, 561 bromocolchicine as a iabei for tubuiin, 46, 567. 

Peters KP, Fauck J, Frommel C (1996) The automatic search for ligand binding sites in proteins of known three-dimensional structure using only geometric criteria. J Mol Biol 256 201-213... 

KaKdas Y, Chandra N (2008) PocketDepth a new depth based algorithm for identification of ligand binding sites in proteins. J Struct Biol 161 31-42... 

Harris R, Olson AJ, Goodsell DS (2008) Automated prediction of ligand-binding sites in proteins. Proteins 70 1506-1517... 

Brakoulias A, Jackson RM (2004) Towards a structural classification of phosphate binding sites in protein-nucleotide complexes an automated all-against-all structural comparison using geometric matching. Proteins Struct Funct Bioinformatics 56 250-260... 

Example 1 Using ACE to Determine the Heparin-Binding Site in Proteins... 

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