Information on EC 3.4.13.19 - membrane dipeptidase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
3.4.13.19
-
RECOMMENDED NAME
GeneOntology No.
membrane dipeptidase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hydrolysis of dipeptides
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
leukotriene biosynthesis
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
43 kDa renal band 3-related protein
-
-
-
-
aminodipeptidase
-
-
-
-
aminodipeptidase
-
-
dehydropeptidase I (DPH I)
-
-
-
-
DHP-I
-
-
-
-
dipeptidase
-
-
-
-
dipeptidase
-
capable of hydrolyzing a range of dipeptides but not tri- and tetrapeptides, p-nitroanilide derivatives of amino acids, or N- or C-terminus-blocked dipeptides
dipeptidase
-
capable of hydrolyzing a range of dipeptides but not tri- and tetrapeptides, p-nitroanilide derivatives of amino acids, or N- or C-terminus-blocked dipeptides
-
dipeptide hydrolase
-
-
-
-
dipeptidyl hydrolase
-
-
-
-
EC 3.4.13.11
-
-
formerly
-
EC 3.4.13.11
-
formerly
EC 3.4.13.11
-
formerly
EC 3.4.13.11
Lactobacillus sanfranciscensis DSM20451
-
formerly
-
glycosyl-phosphatidylinositol-anchored renal dipeptidase
-
-
-
-
GPI-renal dipeptidase
-
-
lysosomal dipeptidase
-
-
MBD
-
-
-
-
MBD-1
-
-
-
-
MBD-2
-
-
-
-
MBD-3
-
-
-
-
MDP
-
-
-
-
MDP
-
-
membrane-associated dipeptidase
-
-
microsomal MBD
-
-
nonspecific dipeptidase
-
-
-
-
nonspecific dipeptidase
-
-
PepV
Lactobacillus sanfranciscensis DSM20451
-
-
-
RDP
-
-
-
-
RDPase
-
-
renal dipeptidase
-
-
-
-
renal dipeptidase
-
-
Ser-Met dipeptidase
-
original name
tissue carnosinase
-
previously named
CAS REGISTRY NUMBER
COMMENTARY
9031-99-6
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain BORI
-
-
Manually annotated by BRENDA team
prolinase and non-specific dipeptidase in human kidney are due to a single enzyme
-
-
Manually annotated by BRENDA team
strains DSM 15814T, CD76, CR20, CF51, CI35, and CM17
-
-
Manually annotated by BRENDA team
Lactobacillus sanfranciscensis DSM20451
strain DSM20451
-
-
Manually annotated by BRENDA team
membrane-bound dipeptidase-1, membrane-bound dipeptidase-2, membrane-bound dipeptidase-3
-
-
Manually annotated by BRENDA team
with selective genetic inactivation of the dicarboxypeptidase activity of testis angiotensin-converting enzyme
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-
glutathione metabolism
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2R)-2-[[(2S)-2-amino-3-cyclohexylpropanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]-2-methylpropanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2R,3S)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]butanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2R,3S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]butanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2R,3S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]butanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2S)-2-[[(2S)-2-amino-3-cyclohexylpropanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]-2-methylpropanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2S)-2-[[(2S)-2-amino-3-cyclohexylpropanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]propanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2S,3S)-2-[[(2S)-2-amino-3-biphenyl-4-ylpropanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]butanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2S,3S)-2-[[(2S)-2-amino-3-cyclohexylpropanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]-4-methylpentanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2S,3S)-2-[[(2S)-2-amino-3-cyclohexylpropanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]butanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2S,3S)-2-[[(2S)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]butanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2S,3S)-2-[[(2S)-3-cyclohexyl-2-(dimethylamino)propanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]butanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2S,3S)-2-[[(2S)-3-cyclohexyl-2-(formylamino)propanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]butanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
(2S,3S)-2-[[(2S)-3-cyclohexyl-2-(methylamino)propanoyl]amino]-3-[([1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylidenetetrahydrofuran-2-yl]-2-oxo-1,2-dihydropyrimidin-4-yl]carbamoyl)oxy]butanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
Ala-Ala + H2O
Ala + Ala
show the reaction diagram
-
-
-
-
?
Ala-Ala + H2O
Ala + Ala
show the reaction diagram
-
-
-
-
?
Ala-Ala + H2O
Ala + Ala
show the reaction diagram
-
62.5% activity compared to Ala-Gln
-
-
?
Ala-Gln + H2O
Ala + Gln
show the reaction diagram
-
100% activity
-
-
?
Ala-Gly + H2O
Ala + Gly
show the reaction diagram
-
68.9% activity compared to Ala-Gln
-
-
?
Ala-Leu + H2O
Ala + Leu
show the reaction diagram
-
14.0% activity compared to Ala-Gln
-
-
?
Ala-Met + H2O
Ala + Met
show the reaction diagram
-
-
-
-
?
Ala-Phe + H2O
Ala + Phe
show the reaction diagram
-
14.0% activity compared to Ala-Gln
-
-
?
Arg-Phe + H2O
Arg + Phe
show the reaction diagram
-
6.3% activity compared to Ala-Gln
-
-
?
Asp-Phe + H2O
Asp + Phe
show the reaction diagram
-
4.9% activity compared to Ala-Gln
-
-
?
B-type natriuretic peptide 1-32 + H2O
B-type natriuretic peptide 3-32 + ?
show the reaction diagram
-
-
-
-
?
beta-lactam + H2O
?
show the reaction diagram
-
-
-
-
?
D-Ala-D-Ala + H2O
D-Ala + D-Ala
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
D-Ala-L-Ala + H2O
D-Ala + L-Ala
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
gamma-L-glutamyl-L-cysteine + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Ala + H2O
Gly + Ala
show the reaction diagram
-
L-Ala and D-Ala
-
-
?
Gly-D-Leu + H2O
Gly + D-Leu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
Gly-D-Phe + H2O
Gly + D-Phe
show the reaction diagram
-
-
-
-
?
Gly-D-Phe + H2O
Gly + D-Phe
show the reaction diagram
-
-
-
?
Gly-D-Phe + H2O
Gly + D-Phe
show the reaction diagram
-
-
-
-
?
Gly-Gly + H2O
Gly + Gly
show the reaction diagram
-
-
-
-
?
Gly-Gly + H2O
Gly + Gly
show the reaction diagram
-
-
-
-
?
Gly-Gly + H2O
Gly + Gly
show the reaction diagram
-
-
-
-
?
Gly-Leu + H2O
Gly + Leu
show the reaction diagram
-
-
-
-
?
Gly-Leu + H2O
Gly + Leu
show the reaction diagram
-
best substrate
-
-
?
Gly-Phe + H2O
Gly + Phe
show the reaction diagram
-
-
-
-
?
Gly-Trp + H2O
Gly + Trp
show the reaction diagram
-
-
-
-
?
Gly-Val + H2O
Gly + Val
show the reaction diagram
-
-
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
L-Ala-D-Ala + H2O
L-Ala + D-Ala
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Ala-Gly + H2O
L-Ala + Gly
show the reaction diagram
-
-
-
-
?
L-Ala-Gly + H2O
L-Ala + Gly
show the reaction diagram
-
-
-
-
?
L-Ala-L-Ala + H2O
L-Ala + L-Ala
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Ala-L-Arg + H2O
L-Ala + L-Arg
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Ala-L-Asp + H2O
L-Ala + L-Asp
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Ala-L-Gln + H2O
L-Ala + L-Gln
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Ala-L-Glu + H2O
L-Ala + L-Glu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Ala-L-His + H2O
L-Ala + L-His
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Ala-L-Lys + H2O
L-Ala + L-Lys
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Arg-D-Asp + H2O
L-Arg + D-Asp
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Arg-Gly + H2O
L-Arg + Gly
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Arg-L-Asp + H2O
L-Arg + L-Asp
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Asn-D-Glu + H2O
L-Asn + D-Glu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-cysteinylglycine + H2O
?
show the reaction diagram
-
-
-
-
?
L-cystinyl-bis-glycine + H2O
?
show the reaction diagram
-
-
-
-
?
L-cystinyl-bis-glycine + H2O
?
show the reaction diagram
-
-
-
-
?
L-cystinyl-bis-glycine + H2O
?
show the reaction diagram
-
membrane-bound dipeptidase-2 cleaves leukotriene D4 but not cystinyl-bis-glycine while membrane-bound dipeptidase-3 cleaves cystinyl-bis-glycine but not LTD4
-
-
?
L-Leu-D-Ala + H2O
L-Leu + D-Ala
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Leu-D-Glu + H2O
L-Leu + D-Glu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Leu-D-Leu + H2O
L-Leu + D-Leu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Leu-D-Ser + H2O
L-Leu + D-Ser
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Leu-L-Asp + H2O
L-Leu + L-Asp
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Leu-L-Leu + H2O
L-Leu + L-Leu
show the reaction diagram
-
-
-
-
?
L-Leu-L-Leu + H2O
L-Leu + L-Leu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Met-D-Glu + H2O
L-Met + D-Glu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Met-D-Leu + H2O
L-Met + D-Leu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Met-L-Leu + H2O
L-Met + L-Leu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
L-Ser-Gly + H2O
L-Ser + Gly
show the reaction diagram
-
-
-
-
?
L-Tyr-D-Leu + H2O
L-Tyr + D-Leu
show the reaction diagram
-
assay at 30C, pH 7.5
-
-
?
Leu-Gly + H2O
Leu + Gly
show the reaction diagram
-
-
-
-
?
Leu-Gly + H2O
Leu + Gly
show the reaction diagram
-
-
-
-
?
Leu-Leu + H2O
Leu + Leu
show the reaction diagram
-
-
-
-
?
Leu-Leu + H2O
Leu + Leu
show the reaction diagram
-
-
-
-
?
Leu-Leu + H2O
Leu + Leu
show the reaction diagram
-
71% activity compared to Ala-Gln
-
-
?
Leu-Leu + H2O
Leu + Leu
show the reaction diagram
Lactobacillus sanfranciscensis DSM20451
-
-
-
-
?
Leu-Phe + H2O
Leu + Phe
show the reaction diagram
-
12.5% activity compared to Ala-Gln
-
-
?
Leu-Trp + H2O
Leu + Trp
show the reaction diagram
-
10.2% activity compared to Ala-Gln
-
-
?
leukotriene D4 + H2O
?
show the reaction diagram
-
membrane-bound dipeptidase-2 cleaves leukotriene D4 but not cystinyl-bis-glycine while membrane-bound dipeptidase-3 cleaves cystinyl-bis-glycine but not LTD4
-
-
?
leukotriene D4 + H2O
?
show the reaction diagram
-
the enzyme is involved in the reanal metabolism of glutathione and its conjugates such as leukotriene
-
-
?
leukotriene D4 + H2O
leukotriene E4
show the reaction diagram
P16444
-
-
-
?
Lys-Gly + H2O
Lys + Gly
show the reaction diagram
-
-
-
-
?
Met-Met + H2O
Met + Met
show the reaction diagram
-
-
-
-
?
N-acylated carbapenems + H2O
?
show the reaction diagram
-
-
-
-
?
N-formimidoyl thienamycin + H2O
?
show the reaction diagram
-
-
-
-
?
N-formimidoyl thienamycin derivative MK0787 + H2O
?
show the reaction diagram
-
hydrolysis of the beta-lactam ring
-
-
?
N-[([(1S,2R)-2-[(3-cyclohexyl-L-alanyl)amino]-3-hydroxy-1-methylpropyl]oxy)carbonyl]-2'-deoxy-2'-methylidenecytidine + H2O
?
show the reaction diagram
-
-
-
-
?
N-[([(1S,2S)-2-[(3-cyclohexyl-L-alanyl)amino]-1,4-dimethyl-3-oxopentyl]oxy)carbonyl]-2'-deoxy-2'-methylidenecytidine + H2O
?
show the reaction diagram
-
-
-
-
?
nonbasic N-acylated thienamycin + H2O
?
show the reaction diagram
-
-
-
-
?
Phe-Ala + H2O
Phe + Ala
show the reaction diagram
-
6.7% activity compared to Ala-Gln
-
-
?
Phe-Gly + H2O
Phe + Gly
show the reaction diagram
-
-
-
-
?
Phe-Gly + H2O
Phe + Gly
show the reaction diagram
-
74.1% activity compared to Ala-Gln
-
-
?
Phe-Tyr + H2O
Phe + Tyr
show the reaction diagram
-
-
-
-
?
pro-B-type natriuretic peptide 1-108 + H2O
pro-B-type natriuretic peptide 3-108 + ?
show the reaction diagram
-
-
-
-
?
S-N-ethylmaleimide-L-cysteinyl-glycine + H2O
?
show the reaction diagram
-
-
-
-
?
thienamycin + H2O
?
show the reaction diagram
-
hydrolysis of the beta-lactam ring
-
-
?
Trp-Gly + H2O
Trp + Gly
show the reaction diagram
-
-
-
-
?
Tyr-Leu + H2O
Tyr + Leu
show the reaction diagram
-
9.5% activity compared to Ala-Gln
-
-
?
Tyr-Phe + H2O
Tyr + Phe
show the reaction diagram
-
3.8% activity compared to Ala-Gln
-
-
?
Val-Gly + H2O
Val + Gly
show the reaction diagram
-
-
-
-
?
Met-Met + H2O
Met + Met
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
broad specificity, no esterase activity, no hydrolysis of proteins
-
-
-
additional information
?
-
-
no hydrolysis of L-Asp-Gly
-
-
-
additional information
?
-
-
no hydrolysis of tripeptides
-
-
-
additional information
?
-
-
no hydrolysis of proline-containing peptides, no hydrolysis of glutathione
-
-
-
additional information
?
-
-
no hydrolysis of leucinamide
-
-
-
additional information
?
-
-
no hydrolysis of D-leucylglycine, no hydrolysis of L-alanyl-glycylglycine, no hydrolysis of L-serylglycylglycine, no hydrolysis of L-leucylglycylglycine
-
-
-
additional information
?
-
-
the enzyme also has beta-lactamase activity
-
-
-
additional information
?
-
-
the enzyme also has beta-lactamase activity
-
-
-
additional information
?
-
-
no hydrolysis of L-Val-Gly
-
-
-
additional information
?
-
-
no reaction with leucinamide
-
-
-
additional information
?
-
-
requires the N-terminal amino acid of the dipeptide in the L-configuration
-
-
-
additional information
?
-
-
enzyme prefers substrates with bulky, hydrophobic group of the dipeptide located at the N-terminal position
-
-
-
additional information
?
-
-
no hydrolysis of D-Ala-Gly
-
-
-
additional information
?
-
-
the enzyme is involved in hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics
-
-
-
additional information
?
-
-
the enzyme might play an important role in the metabolism of glutathione and leukotriene
-
-
-
additional information
?
-
-
does not hydrolyze gamma-L-glutamyl-p-nitroanilide
-
-
-
additional information
?
-
-
low activity toward dipeptides containing aromatic amino acids except for Phe-Gly, does not hydrolyze Leu-Asp, Phe-Phe, or N- or C-terminus-blocked dipeptides (N-carbobenzyloxy-Phe-Gly, N-carbobenzyloxy-Ala-Leu, or Leu-Leu-amide), does not hydrolyze tri-, tetra-, or pentapeptides or p-nitroanilide derivatives of dipeptides and peptides
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
leukotriene D4 + H2O
?
show the reaction diagram
-
the enzyme is involved in the reanal metabolism of glutathione and its conjugates such as leukotriene
-
-
?
additional information
?
-
-
the enzyme is involved in hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics
-
-
-
additional information
?
-
-
the enzyme might play an important role in the metabolism of glutathione and leukotriene
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Cd2+
-
1 mM, activates
Co2+
-
activates
Co2+
-
a cobalt dipeptidase is prepared which contains 2 gatom of cobalt per mol of enzyme which exhibits 42% of the specific activity of the native zinc enzyme
Co2+
-
activates,substitution of Co2+ for Zn2+ considerably lowers the thermostability of the enzyme without affecting the overall conformation of the protein
Co2+
-
addition of Co2+ restores activity after partially inhibition with EDTA
Mn2+
-
activates
Mn2+
-
activates; the Mn-reconstituted enzyme has nearly twice the activity of the original Zn-enzyme, substitution of Mn2+ for Zn2+ considerably loweres the thermostability of the enzyme without affecting the overall conformation of the protein
Mn2+
-
addition of Mn2+ restores activity partially after inhibition EDTA
Zinc
-
enzyme contains about 2 Zn per subunit
Zinc
-
contains 1 mol of zinc per mol of enzyme; contains 1 mol of zinc per mol of enzyme of MW 47200; no absolute specificity for Zn2+ activation
Zinc
-
contains 1 mol of zinc per mol of enzyme
Zinc
-
contains 3.9 gatom of zinc per mol of enzyme
Zinc
-
2.04 g-atom of zinc per mol of enzyme of MW 94000 Da
Zinc
-
the metalloenzyme contains 1 gatom of zinc per mol of subunit, the prosthetic Zn plays dual roles in conformational stability and catalysis of the thermostable dipeptidase
Zinc
-
the active site in each of the (alpha/beta)8 barrel subunits of the homodimer molecule is composed of binuclear zinc ions bridged by the Glu125 side-chain located at the bottom of the barrel
Zn2+
P16444
zinc metalloprotein
Zn2+
-
includes a bis-zinc-containing active center, in which both zinc ions have catalytic properties, folding efficiency is not improved by including up to 25 mM ZnCl2 in the folding buffer, but concentrations above 50 mM ZnCl2 cause precipitation of the protein
Zn2+
-
addition of Zn2+ restores activity after partially inhibition with EDTA
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2Z)-2-[[(1-amino-2-cyclohexylethyl)(hydroxy)phosphoryl]methyl]-3-(4-(trifluoromethyl)phenyl)acrylic acid
-
50% inhibition at 10 nM
(2Z)-2-[[(1-amino-2-cyclohexylethyl)(hydroxy)phosphoryl]methyl]-3-(4-bromophenyl)acrylic acid
-
50% inhibition at 6 nM
(2Z)-2-[[(1-amino-2-cyclohexylethyl)(hydroxy)phosphoryl]methyl]-3-(4-fluorophenyl)acrylic acid
-
50% inhibition at 5 nM
(2Z)-2-[[(1-amino-2-cyclohexylethyl)(hydroxy)phosphoryl]methyl]-3-(4-iodophenyl)acrylic acid
-
50% inhibition at 8 nM
1,10-phenanthroline
-
ZnSO4 restores activity
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
acetate
-
-
bestatin
-
no inhibition
bestatin
-
non-competitive
Cilastatin
-
competitive
Cilastatin
-
-
Cilastatin
P16444
high-affinity reversible inhibitor
Cystinyl-bis-glycine
-
inhibition above 0.2 mM, substrate below
Dansylethylenediamine
-
cilastatin protects
DTT
-
reversible, competitive
EDTA
-
87% inhibition at 1 mM
guanosine triphosphate
-
-
N-bromosuccinimide
-
-
N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline
-
cilastatin protects
N-ethylmaleimide
-
22% inhibition at 1 mM
Nucleotides
-
-
-
p-hydroxymercuribenzoate
-
-
Phenylmethylsulfonylfluoride
-
41% inhibition at 1 mM
phosphate
-
-
phosphinate mimic of L-Ala-D-Asp
-
-
Pro-Ala
-
competitive to hydrolysis of Gly-Leu
thiol compounds
-
-
Z-2-(2,2-Dimethylcyclopropanecarboxamido)-2-butenoic acid
-
-
additional information
-
inhibition by monovalent cations in decreasing order CN-, SCN-, N3-, I-, NO3-, HCO3-, Br-, OAc-, Cl-, F-
-
additional information
-
importance of Glu25 in the catalytic activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Insulin
-
stimulates indirectly the release of RDPase in association with Ca2+ in a concentration-dependent manner (half maximal release at 0.58 nM)
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.111
-
beta-lactam
-
membrane-bound dipeptidase-1
0.65
-
Cystinyl-bis-glycine
-
-
0.77
-
Gly-D-Phe
-
-
6.25
-
Gly-D-Phe
-
mutant enzyme H128L
7.1
-
Gly-D-Phe
-
wild-type enzyme
12.5
-
Gly-D-Phe
-
mutant enzyme H49K
1.22
-
Gly-L-Leu
-
-
0.99
-
Gly-L-Phe
-
-
2.03
-
Gly-L-Trp
-
-
11
-
Gly-L-Val
-
-
0.79
-
Gly-Leu
-
-
0.102
-
glycyldehydrophenylalanine
-
-
1
-
glycyldehydrophenylalanine
-
-
4.4
-
L-Ala-D-Ala
-
pH 7.5, 30C
0.8
-
L-Ala-Gly
-
-
13.8
-
L-Ala-L-Asp
-
pH 7.5, 30C
16
-
L-Ala-L-Gln
-
pH 7.5, 30C
9.5
-
L-Ala-L-Glu
-
pH 7.5, 30C
0.14
-
L-Arg-D-Asp
-
-
1.8
-
L-Arg-L-Asp
-
wild-type enzyme, pH 7.5, 30C
4.3
-
L-Arg-L-Asp
-
mutant H150A, pH 7.5, 30C
4.9
-
L-Arg-L-Asp
-
mutant H150N, pH 7.5, 30C
8.8
-
L-Arg-L-Asp
-
mutant R223K, pH 7.5, 30C
2.4
-
L-Asn-D-Glu
-
pH 7.5, 30C
1.51
-
L-cysteinylglycine
-
-
0.45
-
L-cystinyl-bis-Gly
-
membrane-bound dipeptidase-1
0.6
-
L-cystinyl-bis-Gly
-
-
2.5
-
L-cystinyl-bis-Gly
-
membrane-bound dipeptidase-3
0.75
-
L-Leu-D-Ala
-
-
0.55
-
L-Leu-D-Glu
-
pH 7.5, 30C
0.37
-
L-Leu-D-Leu
-
pH 7.5, 30C
2
-
L-Leu-D-Ser
-
pH 7.5, 30C
0.21
-
L-Leu-Gly
-
-
2
-
L-Leu-L-Asp
-
pH 7.5, 30C
0.056
-
L-Leu-L-Leu
-
enzyme form F
0.086
-
L-Leu-L-Leu
-
enzyme form S
1.4
-
L-Leu-L-Leu
-
pH 7.5, 30C
0.89
-
L-Met-D-Glu
-
pH 7.5, 30C
0.56
-
L-Met-D-Leu
-
pH 7.5, 30C
2.3
-
L-Met-L-Leu
-
pH 7.5, 30C
0.67
-
L-Phe-Gly
-
-
0.15
-
L-Trp-Gly
-
-
0.17
-
L-Tyr-D-Leu
-
pH 7.5, 30C
0.09
-
L-Val-Gly
-
-
0.005
-
leukotriene D4
-
membrane-bound dipeptidase-2
0.01
-
leukotriene D4
-
membrane-bound dipeptidase-1
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
750
-
L-Ala-D-Ala
-
pH 7.5, 30C
1400
-
L-Ala-L-Asp
-
pH 7.5, 30C
140
-
L-Ala-L-Gln
-
pH 7.5, 30C
220
-
L-Ala-L-Glu
-
pH 7.5, 30C
0.4
-
L-Arg-L-Asp
-
mutant R223K, pH 7.5, 30C
0.7
-
L-Arg-L-Asp
-
mutant H150N, pH 7.5, 30C
7.2
-
L-Arg-L-Asp
-
mutant H150A, pH 7.5, 30C
132
-
L-Arg-L-Asp
-
wild-type enyzme, pH 7.5, 30C
288
-
L-Asn-D-Glu
-
pH 7.5, 30C
160
-
L-Leu-D-Ala
-
-
135
-
L-Leu-D-Glu
-
pH 7.5, 30C
21
-
L-Leu-D-Leu
-
pH 7.5, 30C
400
-
L-Leu-D-Ser
-
pH 7.5, 30C
160
-
L-Leu-L-Asp
-
pH 7.5, 30C
140
-
L-Leu-L-Leu
-
pH 7.5, 30C
340
-
L-Met-D-Glu
-
pH 7.5, 30C
194
-
L-Met-D-Leu
-
pH 7.5, 30C
310
-
L-Met-L-Leu
-
pH 7.5, 30C
24
-
L-Tyr-D-Leu
-
pH 7.5, 30C
107
-
L-Arg-D-Asp
-
-
additional information
-
L-Arg-L-Asp
-
mutant D22H, value below 0.03, pH 7.5, 30C; mutant D320A, value below 0.03, pH 7.5, 30C; mutant D320N, value below 0.03, pH 7.5, 30C; mutant R223M, value below 0.03, pH 7.5, 30C
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.13
-
D-Ala-D-Ala
-
pH 7.5, 30C
9040
0.0022
-
D-Ala-L-Ala
-
pH 7.5, 30C
9047
33
-
Gly-D-Leu
-
pH 7.5, 30C
10984
170
-
L-Ala-D-Ala
-
pH 7.5, 30C
12026
14
-
L-Ala-L-Ala
-
pH 7.5, 30C
12031
0.18
-
L-Ala-L-Arg
-
pH 7.5, 30C
12037
100
-
L-Ala-L-Asp
-
pH 7.5, 30C
302490
8.4
-
L-Ala-L-Gln
-
pH 7.5, 30C
302492
24
-
L-Ala-L-Glu
-
pH 7.5, 30C
302491
0.45
-
L-Ala-L-His
-
pH 7.5, 30C
33120
0.072
-
L-Ala-L-Lys
-
pH 7.5, 30C
302837
760
-
L-Arg-D-Asp
-
pH 7.5, 30C
302483
22
-
L-Arg-Gly
-
pH 7.5, 30C
302836
0.046
-
L-Arg-L-Asp
-
mutant R223K, pH 7.5, 30C
12088
0.14
-
L-Arg-L-Asp
-
mutant H150N, pH 7.5, 30C
12088
1.7
-
L-Arg-L-Asp
-
mutant H150A, pH 7.5, 30C
12088
72
-
L-Arg-L-Asp
-
wild-type enzyme, pH 7.5, 30C
12088
120
-
L-Asn-D-Glu
-
pH 7.5, 30C
302489
210
-
L-Leu-D-Ala
-
pH 7.5, 30C
302482
250
-
L-Leu-D-Glu
-
pH 7.5, 30C
302486
56
-
L-Leu-D-Leu
-
pH 7.5, 30C
12280
200
-
L-Leu-D-Ser
-
pH 7.5, 30C
302487
83
-
L-Leu-L-Asp
-
pH 7.5, 30C
207860
100
-
L-Leu-L-Leu
-
pH 7.5, 30C
12285
380
-
L-Met-D-Glu
-
pH 7.5, 30C
302484
350
-
L-Met-D-Leu
-
pH 7.5, 30C
302485
140
-
L-Met-L-Leu
-
pH 7.5, 30C
207853
150
-
L-Tyr-D-Leu
-
pH 7.5, 30C
302488
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.44
-
-
purified enzyme
21
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
0.71 units/mg from cell extract, 77.2 units/mg after 109fold purification, one unit is defined as that required to increase the absorbance by one unit per minute
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.5
-
-
assay at
7.6
-
-
glycyldehydrophenylalanine
9
11
-
enzyme form S
9
-
-
enzyme form F
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
40
-
-
enzyme form S
70
-
-
enzyme form F
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.7
4.8
-
-
4.89
-
-
-
5.4
-
-
-
5.4
-
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
high expression of membrane-bound dipeptidase-1 and membrane-bound dipeptidase-2, expression of membrane-bound dipeptidase-3 is not detectable
Manually annotated by BRENDA team
-
of animals orally exposed to different doses of cadmium for one month. Activity of enzyme as well as carboxypeptidase A and Na+/K+ ATPase in the mucosa of the proximal end of the small intestine are dose-dependently reduced after exposure. In the distal small intestine, enzyme activities are almost restored
Manually annotated by BRENDA team
-
brush-border region of the proximal tubules
Manually annotated by BRENDA team
-
high expression of membrane-bound dipeptidase-1, expression of membrane-bound dipeptidase-2 and membrane-bound dipeptidase-3 is not detectable
Manually annotated by BRENDA team
-
expression of membrane-bound dipeptidase-3 is not detectable, weak expression of membrane-bound dipeptidase-1 and membrane-bound dipeptidase-2
Manually annotated by BRENDA team
-
high expression of membrane-bound dipeptidase-1 and membrane-bound dipeptidase-2, expression of membrane-bound dipeptidase-3 is not detectable
Manually annotated by BRENDA team
-
expression of membrane-bound dipeptidase-3 is not detectable, weak expression of membrane-bound dipeptidase-1 and membrane-bound dipeptidase-2
Manually annotated by BRENDA team
-
expression of membrane-bound dipeptidase-1 and membrane-bound dipeptidase-3 is not detectable, weak activity of membrane-bound dipeptidase-2
Manually annotated by BRENDA team
-
membrane-bound dipeptidase-3 is detected only in testis, membrane-bound dipeptidase-1 and membrane-bound dipeptidase-2 is expressed at high levels
Manually annotated by BRENDA team
-
selective genetic inactivation of the dicarboxypeptidase activity of testis angiotensin-converting enzyme
Manually annotated by BRENDA team
additional information
-
no expression of membrane-bound dipeptidase-1, -3 and -3 in brain
Manually annotated by BRENDA team
additional information
-
not found in liver or hematopoietic progenitor cells such as colony-forming units of granulocyte-macrophage
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
anchoring site
Manually annotated by BRENDA team
-
membrane-bound dipeptidase-1, membrane-bound dipeptidase-2, membrane-bound dipeptidase-3
Manually annotated by BRENDA team
-
plasma membrane
Manually annotated by BRENDA team
-
the active site faces towards the microvillar membrane of a kidney tubule
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Rhodobacter sphaeroides (strain ATCC 17023 / 2.4.1 / NCIB 8253 / DSM 158)
Rhodobacter sphaeroides (strain ATCC 17023 / 2.4.1 / NCIB 8253 / DSM 158)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
47200
-
-
approach to equilibrium measurement
49000
-
-
native enzyme, SDS-PAGE
64680
-
-
LTQ mass spectrometry
87000
93000
-
sedimentation equilibrium measurement, gel filtration
94000
96000
-
gel filtration
95300
-
-
sedimentation equilibrium analysis
100000
-
-
gel filtration
100000
-
-
SDS-PAGE
105000
-
-
gel filtration
130000
-
-
SDS-PAGE under nonreducing conditions
135000
-
-
enzyme form F, gel filtration
180000
-
-
gel filtration
200000
-
-
enzyme form S, gel filtration
218000
-
-
gel filtration
220000
-
-
HPLC gel filtration
320000
-
-
gel filtration
330000
-
-
SDS-PAGE
additional information
-
-
primary structure
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 47000, SDS-PAGE
dimer
-
2 * 50000, SDS-PAGE
dimer
-
2 * 59000, SDS-PAGE
dimer
-
2 * 48600, electrophoresis under reducing conditions
dimer
-
2 * 62000, SDS-PAGE under reducing conditions
dimer
-
2 * 45000, SDS-PAGE under reducing conditions (MW 80000 Da: SDS-PAGE under nonreducing conditions)
dimer
-
2 * 49500, SDS-PAGE
dimer
-
1 * 94000 + 1 * 115000, enzyme form S, SDS-PAGE; 2 * 66000, enzyme form F, SDS-PAGE
dimer
-
-
homohexamer
-
6 * 53333, gel filtration; 6 * 55000, SDS-PAGE
tetramer
-
4 * 59000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
-
N-linked glycosylation; the enzyme has a C-terminal, glycosyl-phosphatidylinositol anchor
glycoprotein
-
structure of the glycosyl-phosphatidylinositol anchors of porcine and human enzyme
glycoprotein
-
membrane-bound dipeptidase-2 and membrane-bound dipeptidase-3 are membrane-bound through a glycosylphosphatidyl-inositol linkage
glycoprotein
-
-
glycoprotein
-
the enzyme is anchored to the microvillar membrane by covalently attached phosphatidylinositol
glycoprotein
-
the enzyme has a C-terminal, glycosyl-phosphatidylinositol anchor; two N-linked glycosylation sites
glycoprotein
-
the enzyme has a C-terminal, glycosyl-phosphatidylinositol anchor
glycoprotein
-
structure of the glycosyl-phosphatidylinositol anchors of porcine and human enzyme
glycoprotein
-
-
additional information
-
not a glycoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
10
-
very low activity (less than about 10%) is observed below pH 5.5, at pH 10.0 the activity is about 50% of the maximum, the enzyme is stable for 30 min over the pH range 4.0 to 8.0
5
-
-
inactivation below
6
-
-
unstable below, both enzyme forms
8
-
-
stable at
8
-
-
both enzyme forms stable
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
70
-
the enzyme shows about 30% and 50% of the maximum activity at 20C and 70C, respectively, stable at temperatures up to 70C, but the activity decreased rapidly above 80C
40
-
-
enzyme form S is unstable above
53
-
-
12 min, about 50% loss of activity
60
-
-
enzyme form F is stable up to
70
-
-
30 min, about 15% loss of activity of the native enzyme, about 55% of the activity of the Co2+-reconstituted enzyme, about 75% loss of activity of the Mn2+-reconstituted enzyme
additional information
-
-
substitution of Co2+ or Mn2+ for Zn2+ considerably lowers the thermostability of the enzyme without affecting the overall conformation of the protein
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
substitution of Co2+ or Mn2+ for Zn2+ considerably lowers the thermostability of the enzyme without affecting the overall conformation of the protein
-
extended dialysis against nonchelating buffers does not result in loss of activity
-
no loss of activity upon lyophilization
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 10% (v/v) glycerol, few days, activity is greatly diminished
-
-80C, 10% (v/v) glycerol, few days, activity is greatly diminished
-
4C, 10% (v/v) glycerol, few days, remains stable
-
4C, sterile filtration, stable for 1 year
-
frozen, in dilute solution, 0.13 mg/ml Tris-HCl buffer, pH 8, loses two-third of its activity after 6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant enzyme is purified by nickel-chelating affinity chromatography, wild type enzyme is purified by ammonium sulfate precipitation, DEAE-cellulose column chromatography, and Q-Sepharose column chromatography
-
2 forms different in electrophoretic mobility: form S (slow) and F (fast)
-
partial
-
ultracentrifugation and Superose 12 (10/300) gel filtration
-
Sephadex G-25 gel filtration, Toyopearl Butyl-650M column chromatography, Toyopearl DEAE-650M column chromatography, and Sephacryl S-200 gel filtration
-
ammonium sulfate precipitation, size exclusion chromatography, ion exchange chromatography and gel filtration
-
affinity purification of enzyme solubilized with detergent
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) Codon Plus-RIL cells
-
expressed in Mus musculus
P16444
expression of membrane-bound dipeptidase-2 and membrane-bound dipeptidase-3 in COS cells
-
expression in Escherichia coli BL21
-
expression in Cos-1 cells
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
H413K/H417K
-
catalytic activity reduced to background levels. Animals carrying the mutant enzyme generate 1 embryo from 22 plugged females compared to 153 embryos from 19 females in wild-type. There is no difference in sperm count, morphology or motility after capacitation in mutant animals. While sperm from wild-type males readily binds to the zona pellucida of unfertilized eggs, sperm from homozygous mutant males shows background levels of binding
D22H
-
mutant with no residual enzyme acitvity
D320A
-
mutant with no residual enzyme acitvity
D320N
-
mutant with no residual enzyme acitvity
H150A
-
mutant with more than doubled Km-values
H150N
-
mutant with more than doubled Km-values
R223K
-
mutant with about 3fold reduced activity compared to wild-type enzyme
R223M
-
mutant with no residual enzyme acitvity
H128L
-
mutant enzyme exhibits a specific activity and Km for Gly-D-Phe comparable with that of the wild-type enzyme
H152L
-
inactive mutant enzyme is expressed at the cell surface at equivalent levels to the wild-type, the mutant enzyme fails to bind to cilastatin-Sepharose in contrast to the wild-type enzyme
H198K
-
inactive mutant enzyme is expressed at the cell surface at equivalent levels to the wild-type
H20L
-
inactive mutant enzyme is expressed at the cell surface at equivalent levels to the wild-type
H49K
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mutant enzyme exhibits a specific activity and Km for Gly-D-Phe comparable with that of the wild-type enzyme
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
in 20 mM Tris-HCl, pH 8.0, 500 mM arginine, containing 1 mM reduced glutathione, 0.2 mM oxidized glutathione, and sodium chloride
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APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
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dicarboxypeptidase activity of testis angiotensin-converting enzyme is required for fertility. Animals carrying mutant enzyme without catalytic activity generate 1 embryo from 22 plugged females compared to 153 embryos from 19 females in wild-type
nutrition
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cadmium given in drinking water compromises protein digestion and absorption of nutrients particularly in the proximal region of small intestine