Probing the determinants of protein stability: comparison of class A beta-lactamases.
Five class A beta-lactamases produced by various mesophilic bacterial species have been compared. Although closely related in primary and overall structures, these enzymes exhibit very different stabilities. In order to investigate the factors responsible for these differences, several features deduced from the amino acid composition and three-dimensional structures were studied for the five proteins. This analysis revealed that higher stability appeared to correlate with increased numbers of intramolecular hydrogen bonds and of salt bridges. By contrast, the global hydrophobicity of the protein seemed to play a relatively minor role. A strongly unfavourable balance between charged residues and the presence of a cis-peptide bond preceding a non-proline residue might also contribute to the particularly low stability of two of the enzymes.
Vanhove
M
M
Laboratoire d'Enzymologie and Centre d'Ingénierie des Protéines, Université de Liège, Belgium.
Houba
S
S
b1motte-Brasseur
J
J
Frère
J M
JM
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001419:Bacteria / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D003461:Crystallography; D004795:Enzyme Stability / Q000235:genetics* / Q000502:physiology; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D005658:Fungi / Q000201:enzymology; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013696:Temperature; D013816:Thermodynamics; D001618:beta-Lactamases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism
D000596:Amino Acids; D001426:Bacterial Proteins; D005656:Fungal Proteins; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1