Protein Science, Vol 7, Issue 8 1768-1771, Copyright © 1998 by Cold Spring Harbor Laboratory Press

ARTICLE

Enzyme-mononucleotide interactions: Three different folds share common structural elements for ATP recognition

K. A. DENESSIOUK, J. V. LEHTONEN and M. S. JOHNSON
Department of Biochemistry and Pharmacy, Abo Akademi University, BioCity 3A, P.O. Box 66, FIN-20521 Turku, Finland Centre for Biotechnology, University of Turku and Abo Akademi University, BioCity 5B, FIN-20521 Turku, Finland Moscow Institute of Physics and Technology, 141700, Dolgoprudny, Russia

Three ATP-dependent enzymes with different folds, cAMP-dependent protein kinase, D-Ala:D-Ala ligase and the {alpha}-subunit of the {alpha}(2){beta}(2) ribonucleotide reductase, have a similar organization of their ATP-binding sites. The most meaningful similarity was found over 23 structurally equivalent residues in each protein and includes three strands each from their {beta}-sheets, in addition to a connecting loop. The equivalent secondary structure elements in each of these enzymes donate four amino acids forming key hydrogen bonds responsible for the common orientation of the ``AMP'' moieties of their ATP-ligands. One lysine residue conserved throughout the three families binds the alpha-phosphate in each protein. The common fragments of structure also position some, but not all, of the equivalent residues involved in hydrophobic contacts with the adenine ring. These examples of convergent evolution reinforce the view that different proteins can fold in different ways to produce similar structures locally, and nature can take advantage of these features when structure and function demand it, as shown here for the common mode of ATP-binding by three unrelated proteins.
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