Family M35


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family M35

NamePeptidase family M35 (deuterolysin family)
Family type peptidaseM35.002 - deuterolysin (Aspergillus flavus), MEROPS Accession MER0001394 (peptidase unit: 194-381)
Content of familyPeptidase family M35 contains fungal and bacterial metalloendopeptidases.
History Identifier created: Proteolysis in Cell Function, pp13-21, IOS Press, Amsterdam (1997)
Penicillolysin (M35.001), deuterolysin (M35.002) and peptidyl-Lys metalloendopeptidase (M35.004) have been reviewed (Ichishima, 2004; Tatsumi, 2004; Takio, 2004).
Catalytic typeMetallo
Active site residuesH321 E322 H325 D336 
Active siteFamily M35 members contain two zinc binding histidines and a catalytic glutamate in an HEXXH motif. There is a third zinc ligand, an Asp, found in a GTXDXXYG motif C-terminal to the His zinc ligands (see the Alignment). For this reason the peptidases in this family are sometimes termed 'aspzincins', although peptidases in which the third ligand of zinc is Asp also occur in families M6, M7 and M64.
Activities and specificitiesDeuterolysin (M35.002) and penicillolysin (M35.001) have both been found to be especially active on basic protein substrates such as histones, protamine and salmine (Doi et al., 2003; Ichishima, 2004). A basic residue, Arg or Lys, is commonly prefered in the P1" subsite, and is required by the very selective peptidyl-Lys metalloendopeptidase (M35.004), which cleaves XaaLys bonds, in which Xaa can even be Pro.
InhibitorsChelating agents such as 1,10-phenanthroline inhibit.
Molecular structureThe tertiary structure of peptidyl-Lys metalloendopeptidase contains five alpha helices and four beta strands (Hori et al., 2001). It is reported that the conserved tyrosine, three residues C-terminal to the zinc-binding Asp, acts as a proton donor during catalysis (Hori et al., 2001). The structure of deuterolysin was determined by McAuley et al. (2001). There is no conserved methionine in the "Met-turn" in family M35 unlike other families of subclan MA(M) in clan MA. The structure of the AsaP1 toxin precursor from Aeromonas salmonicida shows that the propeptide inhibits because the side chain of a lysine ooccupies the S1" pocket and interactis with three carboxyate side chains. Mutation studies have shown that the propeptide also acts as a chaperone (<%Bogdanovic et al., 2016[2-160825A262]%>).
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of thermolysin, the type example for clan MA.
Distribution of family Bacteria details  
Archaea -  
Protozoa -  
Fungi details  
Plants -  
Animals details  
Viruses -  
Biological functions
Pharmaceutical and biotech relevanceDeuterolysin plays an important role in producing the distinctive taste of soy sauce by hydrolysis of soybean proteins (Tatsumi, 2004).
Statistics for family M35Sequences:265
Identifiers with PDB entries:3
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
EcpA peptidaseM35.003Yes
peptidyl-Lys metallopeptidaseM35.004Yes
AVR-Pita peptidase (Magnaporthe sp.)M35.005-
family M35 non-peptidase homologuesnon-peptidase homologue-
family M35 unassigned peptidasesunassigned-