Summary for peptidase M20.013: Xaa-methyl-His dipeptidase

Summary Alignment Tree Sequences Sequence features Distribution Literature Substrates

 

Names
MEROPS NameXaa-methyl-His dipeptidase
Other namesaminoacyl-methylhistidine dipeptidase, anserinase, X-methyl-His dipeptidase
Name and HistoryThe enzyme was first discovered as anserinase from codling skeletal muscle (Jones et al., 1955). In a separate line of investigation, the existence of an enzyme deacetylating Nalpha-acetyl-His (called acetylhistidine deacetylase) in fish brain was reported (Baslow et al., 1967). Subsequently, it was revealed that the properties of acetylhistidine deacetylase resembled those of anserinase (Lenney et al., 1978). Both enzymes were, therefore, judged to be the same and renamed Xaa-methyl-His dipeptidase by the IUBMB in 1997.
Domain architecture
MEROPS Classification
Classification Clan MH >> Subclan (none) >> Family M20 >> Subfamily F >> M20.013
HolotypeXaa-methyl-His dipeptidase (Oreochromis niloticus) (peptidase unit: 26-487), MERNUM MER0057434
History Identifier created: MEROPS 7.3 (22 December 2005)
Activity
Catalytic typeMetallo
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.13 (Dipeptidases) >> Peptidase 3.4.13.5
EnzymologyBRENDA database
PreparationThe richest sources of the enzyme are fish brain and fish ocular fluid (Lenney et al., 1978). Exceptionally, some fish species, such as Atlantic cod (Gadus morhua), haddock (Melanogrammus aeglefinus) (Jones et al., 1955) and Japanese eel (Anguilla japonica) (Oku et al., 2012), contain the enzyme activity in their skeletal muscles. The enzyme can be prepared by a combination of routine methods, including ammonium sulfate precipitation, ion-exchange chromatography, gel filtration, hydrophobic interaction chromatography, and chromatofocusing. Preparative electrophoresis is used to obtain a highly purified enzyme (Yamada et al., 2005).
SpecificityBroad specificity on dipeptides and Nalpha-acetylated amino acids. The enzyme is unable to hydrolyze tripeptides (Yamada et al., 1993).
pH optimum7.3 for anserine (Jones et al., 1955) and 6.5 for acetyl-His (Yamada et al., 1993).
Substrate comments
StructureThe active form is a homodimer of approx. 55 kDa subunits (Yamada et al., 1992). The enzyme is a secretory glycoprotein with an N-terminus signal peptide region and N-glycosylation sites (Yamada et al., 2005).
LocationSoluble supernatant fraction in fish brain (Yamada et al., 1993). Fish ocular fuild (Baslow et al., 1967).
PhysiologyThere are two physiological substrates for the enzyme: one is Nalpha-acetyl-His and another is anserine. The former molecule is present in very high concentration ubiquitously both in the brain and the eye lens of ectothermic jawed vertebrates. Xaa-methyl-His dipeptidase, together with histidine N-acetyltransferase (Baslow et al., 1966;Yamada et al., 2014), rapidly turnover (breakdown and synthesize) Nalpha-acetyl-His in the brain and the eye (Baslow et al., 1969).
Biological aspectsThe enzyme is present only in ectothermic jawed vertebrates, including ray-finned fishes, amphibians and reptiles, and completely absent from endothermic vertebrates, including birds and mammals (Oku et al., 2011). Darmin, which is expressed during endoderm development in African clawed frog (Xenopus laevis) (Pera et al., 2003), is the amphibian orthologue of Xaa-methyl-His dipeptidase.
Distinguishing featuresXaa-methyl-His dipeptidase is closely related to carnosine dipeptidase I (M20.006) and carnosine dipeptidase II (M20.005). All three enzymes can cleave certain dipeptides, such as carnosine, anserine, and/or homocarnosine, that are resistant to most other peptidases due to the presence of non-alpha amino acids on the N-terminal side. Xaa-methyl-His dipeptidase can be distinguished from these two enzymes by its ability to deacetylate Nalpha-acetyl-His (Lenney et al., 1990;Jackson et al., 1991;Yamada et al., 2005). Moreover, Xaa-methyl-His dipeptidase is hardly inhibited by 10 micromolar bestatin (Yamada et al., 1993), which is extremely effective against carnosine dipeptidase II (Peppers & Lenney, 1988).
Pathways KEGGbeta-Alanine metabolism
Contributing authorsShoji Yamada, Laboratory of Marine Biochemistry, Faculty of Fisheries, Kagoshima University, 4-50-20 Shimoarata, Kagoshima 890-0056, Japan
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/agScissile bondhgl/-/-/- (based on 13 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 0 0 0 3 3 0 0 0
Pro 0 0 0 1 0 0 0 0
Ala 0 0 0 3 0 0 0 0
Val 0 0 0 0 0 0 0 0
Leu 0 0 0 1 3 0 0 0
Ile 0 0 0 0 0 0 0 0
Met 0 0 0 0 1 0 0 0
Phe 0 0 0 0 0 0 0 0
Tyr 0 0 0 0 0 0 0 0
Trp 0 0 0 0 0 0 0 0
Ser 0 0 0 0 0 0 0 0
Thr 0 0 0 0 0 0 0 0
Cys 0 0 0 0 0 0 0 0
Asn 0 0 0 0 0 0 0 0
Gln 0 0 0 0 0 0 0 0
Asp 0 0 0 0 0 0 0 0
Glu 0 0 0 0 0 0 0 0
Lys 0 0 0 0 0 0 0 0
Arg 0 0 0 0 0 0 0 0
His 0 0 0 0 6 0 0 0