Summary: BlaR1 peptidase M56
BlaR1 peptidase M56 Provide feedback
Production of beta-Lactamase and penicillin-binding protein 2a (which mediate staphylococcal resistance to beta-lactam antibiotics) is regulated by a signal-transducing integral membrane protein and a transcriptional repressor. The signal transducer is a fusion protein with penicillin-binding and zinc metalloprotease domains. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which auto-activates, and the repressor, which is inactivated, unblocking gene transcription. Homologues to this peptidase domain, which corresponds to Merops family M56, are also found in a number of other bacterial genome sequences.
Zhang HZ, Hackbarth CJ, Chansky KM, Chambers HF; , Science 2001;291:1962-1965.: A proteolytic transmembrane signaling pathway and resistance to beta-lactams in staphylococci. PUBMED:11239156 EPMC:11239156
Internal database links
|Similarity to PfamA using HHSearch:||Peptidase_M48|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR008756
In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:
- Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
- Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases.
In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.
Metalloproteases are the most diverse of the four main types of protease, with more than 50 families identified to date. In these enzymes, a divalent cation, usually zinc, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. The known metal ligands are His, Glu, Asp or Lys and at least one other residue is required for catalysis, which may play an electrophillic role. Of the known metalloproteases, around half contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [PUBMED:7674922]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [PUBMED:7674922].
This group of metallopeptidases belong to MEROPS peptidase family M56 (clan M-). The predicted active site residues for members of this family occur in the motif HEXXH. The type example is BlaR1 peptidase from Bacillus licheniformis.
Production of beta-Lactamase and penicillin-binding protein 2a (which mediate staphylococcal resistance to beta-lactam antibiotics) is regulated by a signal-transducing integral membrane protein and a transcriptional repressor. The signal transducer is a fusion protein with penicillin-binding and zinc metalloprotease domains. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which auto-activates, and the repressor, which is inactivated, unblocking gene transcription.
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Clan MA is one of two zinc-dependent metallopeptidases that contain the HEXXH motif. The two histidines are zinc ligands. The structures of this clan show the active site is between its two sub-domains.
The clan contains the following 54 members:Aspzincin_M35 Astacin BSP DUF1570 DUF2201_N DUF2268 DUF3152 DUF3633 DUF3810 DUF4157 DUF45 DUF955 Enhancin HRXXH M60-like Peptidase_M1 Peptidase_M10 Peptidase_M11 Peptidase_M13 Peptidase_M2 Peptidase_M27 Peptidase_M3 Peptidase_M30 Peptidase_M32 Peptidase_M35 Peptidase_M36 Peptidase_M4 Peptidase_M41 Peptidase_M43 Peptidase_M48 Peptidase_M4_C Peptidase_M50 Peptidase_M50B Peptidase_M54 Peptidase_M56 Peptidase_M57 Peptidase_M6 Peptidase_M61 Peptidase_M64 Peptidase_M66 Peptidase_M7 Peptidase_M8 Peptidase_M9 Peptidase_M91 Peptidase_MA_2 Peptidase_U49 Reprolysin Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5 SprT-like WLM Zn_peptidase
We make a range of alignments for each Pfam-A family:
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Curation and family details
|Number in seed:||12|
|Number in full:||1807|
|Average length of the domain:||241.60 aa|
|Average identity of full alignment:||19 %|
|Average coverage of the sequence by the domain:||47.77 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||6|
|Download:||download the raw HMM for this family|
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