Family S16

Family

Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

Summary for family S16

NamePeptidase family S16 (lon protease family)
Family type peptidaseS16.001 - Lon-A peptidase (Escherichia coli), MEROPS Accession MER0000485 (peptidase unit: 537-784)
Content of familyPeptidase family S16 contains endopeptidases, mostly ATP-dependent.
History Identifier created: Biochem.J. 290:205-218 (1993)
In 1978, mutations of the lon gene of Escherichia coli were seen to cause a defect in protein degradation (the 'deg' phenotype: Gottesman & Zipser, 1978). Independently, the first ATP-dependent peptidase to be identified was found in E. coli, and named protease La (Swamy & Goldberg, 1981). It soon became clear that protease La was the product of the lon gene (Charette et al., 1981; Chung & Goldberg, 1981), and the enzyme is now most commonly termed the Lon protease or Lon peptidase. It has homologues in all kinds of organisms.
Catalytic typeSerine
Active site residuesS679 K,R722 
Active siteThere is a catalytic dyad consisting of Ser and Lys residues (see the Alignment). The evidence leading to the identification of the active site residues has been reviewed by Besche & Zwickl (2004) and Botos et al., 2004.
Activities and specificitiesLon peptidase is both an ATP-dependent peptidase and a protein-activated ATPase, because the hydrolysis reactions for peptides and ATP are coupled (Chung & Goldberg, 2004). ADP does not activate, but is an inhibitor that is bound more tightly than ATP. The rate-limiting step in proteolysis is suggested to be the release of the bound ATP that is stimulated by the binding of a protein substrate (Menon & Goldberg, 1987).
Specificity is commonly described as 'chymotrypsin-like', and sites of cleavage of the protein SulA by Lon peptidase show that Leu is the prefered P1 residue (Nishii et al., 2002).
Hydrolysis of peptide substrates such as glutaryl-Ala-Ala-Phe-methoxynaphthylamine (MNA), succinyl-Phe-Leu-Phe-MNA (Waxman & Goldberg, 1985) and Y(NO2)RGITCSGRQK(Abz), is also activated by ATP (Thomas-Wohlever & Lee, 2002).
InhibitorsPinA (I24.001), encoded by bacteriophage T4, is a 19-kDa protein that reversibly inhibits the hydrolysis of proteins, but not peptides, by Lon peptidase (Hilliard et al., 1998). Synthetic inhibitors include Z-Gly-Leu-Phe-chloromethane and DFP (Waxman & Goldberg, 1985).
Molecular structureCrystallographic structures have been determined separately for the ATPase and peptidase domains of E. coli Lon peptidase. The fold of the peptidase domain was found to be quite different from those of other peptidases that have a Ser, Lys catalytic dyad in families S24 and S26 of clan SF (Botos et al., 2004). Accordingly, family S16 is placed in a separate clan SJ.
Forms of Lon peptidase from E. coli and Thermoplasma acidophilum self-assemble into hexameric rings (Besche & Zwickl, 2004), but electron microscopy of the yeast mitochondrial Lon peptidase shows a heptameric complex (Stahlberg et al., 1999).
ClanSJ
Basis of clan assignmentType family of clan SJ.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses details  
Biological functionsThe function of Lon peptidase in bacteria is thought to be the degradation of unfolded proteins (Roudiak et al., 1998). One physiological substrate of Lon peptidase in E. coli is SulA protein, which is a particularly unstable protein that is a cell-division inhibitor (Nishii et al., 2002).
ReviewsBotos et al., 2004
Statistics for family S16Sequences:17814
Identifiers:25
Identifiers with PDB entries:7
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases INTERPRO IPR001984
PANTHER PTHR10046
PANTHER PTHR43718
PFAM PF05362
PFAM PF13541
SCOP 102769
Peptidases and Homologues MEROPS ID Structure
Lon-A peptidaseS16.001Yes
PIM1 peptidaseS16.002Yes
Lon peptidase homologue (type 3)S16.003-
Lon peptidase (type 4)S16.004-
Lon-B peptidaseS16.005Yes
psLon peptidaseS16.006-
LonC peptidaseS16.007Yes
protease La (Methanocaldococcus-type)S16.008Yes
Lon-2 peptidase (bacteria)S16.009-
PIM1 peptidase (Saccharomyces-type)S16.010-
At5g26860 (Arabidopsis thaliana)S16.011-
SepM peptidase (Streptococcus mutans)S16.012Yes
At3g05790 (Arabidopsis thaliana)S16.A02-
At3g05780 (Arabidopsis thaliana)S16.A03-
DNA repair protein RadA (Escherichia coli)S16.A04-
rpb-4 g.p. (Caenorhabditis elegans)S16.A05-
Y75B8A.4 g.p. (Caenorhabditis elegans)S16.A06-
F46F5.5 g.p. (Caenorhabditis elegans)S16.A07-
R13H4.6 g.p. (Caenorhabditis elegans)S16.A08-
C06C3.8 g.p. (Caenorhabditis elegans)S16.A09-
ycbZ (Escherichia coli)S16.A10-
PF0467 (Pyrococcus furiosus)S16.A11Yes
PF1438 (Pyrococcus furiosus)S16.A12-
DDB_G0277307 (Dictyostelium discoideum)S16.A13-
PF14_0147 g.p. (Plasmodium falciparum)S16.A14-
family S16 non-peptidase homologuesnon-peptidase homologue-
family S16 unassigned peptidasesunassigned-