Strain in protein structures as viewed through nonrotameric side chains: II. effects upon ligand binding.
The relation between the spatial positioning of nonrotameric residues and ligands was studied in 112 tertiary structures of protein-ligand complexes with a crystallographic resolution of </= 1. 8 A. Nonrotameric side chains and especially clusters of interacting nonrotameric residues were found to be associated preferentially with ligand- and substrate-binding sites. Asp, Glu, His, Met, and Asn are favored nonrotameric residue types positioned in the first 9-A shell around ligands. Comparison of 20 complexes with associated apo structures suggests that ligand binding induces nonrotamericity and, hence, strain within protein-ligand complexes. The internal energy gain is not neutralized by increased hydrogen bonding or salt-bridge formation involving side chains that become nonrotameric in the complexed structure. It is suggested that the increased internal energy might aid in the formation and ejection of enzymatic products, thereby enhancing activity. These results could prove useful in protein engineering experiments aimed at altering enzymatic activity. Proteins 1999;37:44-55.
Heringa
J
J
Division of Mathematical Biology, National Institute for Medical Research, London, United Kingdom. jhering@nimr.mrc.ac.uk
Argos
P
P
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001059:Apoproteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009038:Motion; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013314:Stress, Mechanical
D000596:Amino Acids; D001059:Apoproteins; D008024:Ligands; D011506:Proteins