Roles for holes: are cavities in proteins mere packing defects?
Vallone, B.; Brunori, M.
Italian Journal of Biochemistry 53(1): 46-52
2004
ISSN/ISBN: 0021-2938 PMID: 15356962 Document Number: 582377
Atomic packing in proteins is not optimized, most structures containing internal cavities, which have been identified by molecular modelling and characterized experimentally. Cavities seem to play a role in assisting conformational changes between domains or subunit interfaces. Comparison between homologous proteins from thermophiles and mesophiles indicates that optimizing packing enhances stabilization at the expense of flexibility. For proteins which interact with small ligands or substrates, cavities seem to play a role in controlling binding and catalysis, rather than being mere "packing defects". We believe that a more complete analysis on the localization, conservation and role of cavities in protein structures (by modelling and site-directed mutagenesis), will reveal that rather than being randomly distributed, they are located in key positions to allow structural dynamics and thereby functional control.