Ligand Selectivity and Competition Between Enzymes in Silico  

Oleh:

Macchiarulo, Antonio ; Nobeli, Irene ; Thornton, Janet M.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Biotechnology: The Science and Business of Biotechnology vol. 22 no. 8 (Agu. 2004), page 1039-1046.
Topik: enzymes; ligand selectivity; enzymes; silico

Ketersediaan

Perpustakaan Pusat (Semanggi) Nomor Panggil: NN9.1 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

In a cell, there are many possibilities for cross interactions between enzymes and small molecules, arising from the similarities in the structures of the metabolites and the flexibility in binding of protein active sites. Despite this promiscuity, the cognate partners must be able to recognize each other in vivo, for the cell to function efficiently. This study examines the basis of their selectivity in recognition using standard docking calculations and finds significant improvement when proteins and ligands are cross-docked. We find that cognate molecules rarely form the most stable complexes and that specificity may be driven either by recognition of the substrate by the enzyme or the recognition of the enzyme by the substrate. Despite limitations of the in silico methods, especially the scoring functions, these calculations highlight the need to consider cross reactions in the cell and suggest that localization and compartmentalization must be important factors in the evolution of complex cells. However the inherent promiscuity of these interactions can also benefit an organism, by facilitating the evolution of new functions from old ones. The results also suggest that high throughput screening should involve not just a panel of small molecules, but also a panel of proteins to test for cross reactivity.

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