Classification of ATP‐dependent proteases Lon and comparison of the active sites of their proteolytic domains

• Published in: European journal of biochemistry Vol. 271; no. 23‐24; pp. 4865 - 4871
• Main Authors: Rotanova, Tatyana V., Melnikov, Edward E., Khalatova, Anna G., Makhovskaya, Oksana V., Botos, Istvan, Wlodawer, Alexander, Gustchina, Alla
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-12-2004
• Subjects: AAA+ proteins; Adenosine Triphosphate - metabolism; Amino Acid Sequence; Base Sequence; Binding Sites; DNA Primers; Evolution, Molecular; Hydrolysis; Lon proteases; LonA and LonB subfamilies; Models, Molecular; Molecular Sequence Data; Protease La - chemistry; Protease La - metabolism; Protein Conformation; proteolytic site; Sequence Homology, Amino Acid; Ser–Lys dyad
• ISSN: 0014-2956; 1432-1033
• DOI: 10.1111/j.1432-1033.2004.04452.x

ATP‐dependent Lon proteases belong to the superfamily of AAA+ proteins. Until recently, the identity of the residues involved in their proteolytic active sites was not elucidated. However, the putative catalytic Ser–Lys dyad was recently suggested through sequence comparison of more than 100 Lon proteases from various sources. The presence of the catalytic dyad was experimentally confirmed by site‐directed mutagenesis of the Escherichia coli Lon protease and by determination of the crystal structure of its proteolytic domain. Furthermore, this extensive sequence analysis allowed the definition of two subfamilies of Lon proteases, LonA and LonB, based on the consensus sequences in the active sites of their proteolytic domains. These differences strictly associate with the specific characteristics of their AAA+ modules, as well as with the presence or absence of an N‐terminal domain.