Family M56

Family

Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family M56

Family type peptidaseM56.001 - BlaR1 peptidase (Staphylococcus aureus), MEROPS Accession MER0014137 (peptidase unit: 1-294)
Content of familyPeptidase family M56 contains membrane-bound bacterial endopeptidases.
History Identifier created: MEROPS 5.7 (17 December 2001)
Staphylococcus species achieve resistance to penicillin through production of a set of gene products, including the beta-lactamase BlaZ, a repressor BlaI and the BlaR1 protein (M56.001). The induction of the lactamase is triggered by the binding of the antibiotic to an extracellular domain of BlaR1. This is followed by cleavage of the BlaR1 molecule and also of the BlaI repressor, which inactivates it allowing expression of the lactamase. MecR1 (M56.002) is one of an homologous set of proteins that allow resistance to the beta-lactamase-stable methicillin.
Catalytic typeMetallo
Active site residuesH201 E202 H205 E242 
Active siteMembers of family M56 contains an HEXXH motif located between the third and fourth transmembrane domains with the third metal ligand predicted by MEROPS to be an Asp located five residues C-terminal to the second zinc-binding His (see the Alignment). Site-directed mutagenesis has shown that His and Glu residues from the consensus sequence are essential for autolysis of BlaR1 and cleavage of the receptor (Zhang et al., 2001).
Activities and specificitiesAutolysis of the BlaR1 precursor occurs at Arg293Arg. Mutation of Arg293 to Ala prevents both autolysis and cleavage of the repressor protein. BlaI is cleaved by activated BlaR1 at Asn101Phe102 (Zhang et al., 2001).
Molecular structureAlthough the putative zinc-binding motif of BlaR1 does not conform to the consensus of Jongeneel (Jongeneel et al., 1989), the family is included in clan MA. The most thoroughly characterised member of family M56 is PenR1 (M56.003) from Bacillus licheniformis (Hardt et al., 1997). In view of their homology, BlaR1 and MecR1 are also thought to be integral membrane proteins with four alpha-helical segments (Zhang & Chambers, 2004). Crystal structures of the sensor domain of BlaR1 have been described (Wilke et al., 2004).
ClanMA
SubclanMA(E)
Basis of clan assignmentFamily M56 is included in clan MA on the basis of comparisons of hidden Markov models derived from the MEROPS family alignments
Distribution of family Bacteria details  
Archaea -  
Protozoa -  
Fungi -  
Plants details  
Animals -  
Viruses details  
Biological functionsThe peptidases of family M56 allow bacteria to respond to the presence of beta-lactam antibiotics by the expression of beta-lactamases and penicillin-binding proteins.
ReviewsBlaR1 and MecR1 have been reviewed by Zhang & Chambers (2004).
Statistics for family M56Sequences:2747
Identifiers:3
Identifiers with PDB entries:2
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
BlaR1 peptidaseM56.001Yes
MecR1 g.p. (Staphylococcus sp.)M56.002-
PenR1 peptidaseM56.003Yes
family M56 non-peptidase homologuesnon-peptidase homologue-
family M56 unassigned peptidasesunassigned-