Any feedback?
Information on EC 3.4.24.16 - neurolysin and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC3.4.24.16Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.4.24.16 neurolysinSpecify your search results
Word Map
- 3.4.24.16
- bradykinin
- metallopeptidase
- metalloendopeptidase
- dynorphins
- pro-ile
-
neuropeptidase
-
pro10-tyr11
-
neuromedin
- hemopressins
-
arg8-arg9
-
non-at2
-
neurotensin-degrading
- molecular biology
- pharmacology
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
neurolysin, ep24.16, endopeptidase 24.16, ep 24.16, mitochondrial peptidase, oligopeptidase m, soluble angiotensin-binding protein, microsomal endopeptidase, neurotensin endopeptidase, soluble angiotensin ii-binding protein, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
endopeptidase 24.16
-
-
-
-
endopeptidase 24.16B
-
-
-
-
MEP
-
-
-
-
Microsomal endopeptidase
-
-
-
-
MOP
-
-
-
-
neurotensin endopeptidase
-
-
-
-
oligopeptidase M
-
-
-
-
peptidase, neurotensin endo
-
-
-
-
peptidase, neurotensin endo-
-
-
-
-
SABP
-
-
-
-
Soluble angiotensin-binding protein
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
149371-24-4
-
90463-53-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys + H2O
?
-
no cleavage
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-Phe + Ser-Pro-Phe-Arg
-
-
-
-
?
Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu + H2O
Asp-Arg-Val-Tyr-Ile-His-Pro + Phe-His-Leu
-
-
-
-
?
FSTSAQNN + H2O
?
octMdh1, Oct1 generated octapeptide from Mus musculus
-
-
?
MFLTRFVGRRFLAAASARS + H2O
MFLTR + FVG + RRFL + 2 L-Ala + ASA + RS
pL29, presequence from Arabidopsis thaliana
-
-
?
MFRRPVLQVLRQFVRH + H2O
MFR + RPVL + QVLR + QFVRH
pSSBP, human presequence
-
-
?
pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu + H2O
pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro + Tyr-Ile-Leu
Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile + H2O
Tyr-Gly-Gly-Phe-Leu + Arg-Arg-Ile
-
-
-
-
?
Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg + H2O
peptide fragments
-
i.e. dynorphin(1-9)
-
-
?
Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln + H2O
peptide fragments
-
-
-
-
?
GlpLYENKPRRPYIL + H2O
GlpLYENKPRRP + YIL
neurotensin, secreted human neuropeptide
-
-
?
GlpLYENKPRRPYIL + H2O
GlpLYENKPRRP + YIL
neurotensin, secreted human neuropeptide, Nln cleaves the Pro10-Tyr11 bond, but not the Arg8-Arg9 bond
-
-
?
pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu + H2O
pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro + Tyr-Ile-Leu
-
specific hydrolysis of the Pro10-Tyr11 bond
-
?
pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu + H2O
pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro + Tyr-Ile-Leu
-
specific hydrolysis of the Pro10-Tyr11 bond
-
?
additional information
?
-
-
the enzyme is active in inactivation of neuropeptides, biological relevance, overview
-
-
?
additional information
?
-
QFS and neurotensin compete for their hydrolysis by enzyme Nln
-
-
?
additional information
?
-
the structure of mitochondrial peptidase neurolysin mutant hNLNE475Q in complex with the products of neurotensin cleavage reveals a closed conformation with an internal cavity that restricts substrate length and highlights the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity. hNLN cooperates with presequence protease (PreP or PITRM1) in the degradation of long targeting peptides and amyloid-beta peptide, Abeta1-40, associated with Alzheimer disease, particularly cleaving the hydrophobic fragment Abeta35-40. No cleavage of amyloid-beta1-40, pACD1 (presequence from Arabidopsis thaliana), SytII 40-60 (non-presequence of synaptotagmin from Rattus norvegicus), pCox4 (presequence from Saccharomyces cerevisiae), pOTC (human presequence), and pF1beta (presequence from NIcotiana plumbaginifolia), mass spectrometric analysis
-
-
?
additional information
?
-
-
the structure of mitochondrial peptidase neurolysin mutant hNLNE475Q in complex with the products of neurotensin cleavage reveals a closed conformation with an internal cavity that restricts substrate length and highlights the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity. hNLN cooperates with presequence protease (PreP or PITRM1) in the degradation of long targeting peptides and amyloid-beta peptide, Abeta1-40, associated with Alzheimer disease, particularly cleaving the hydrophobic fragment Abeta35-40. No cleavage of amyloid-beta1-40, pACD1 (presequence from Arabidopsis thaliana), SytII 40-60 (non-presequence of synaptotagmin from Rattus norvegicus), pCox4 (presequence from Saccharomyces cerevisiae), pOTC (human presequence), and pF1beta (presequence from NIcotiana plumbaginifolia), mass spectrometric analysis
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
FSTSAQNN + H2O
?
octMdh1, Oct1 generated octapeptide from Mus musculus
-
-
?
GlpLYENKPRRPYIL + H2O
GlpLYENKPRRP + YIL
neurotensin, secreted human neuropeptide
-
-
?
MFLTRFVGRRFLAAASARS + H2O
MFLTR + FVG + RRFL + 2 L-Ala + ASA + RS
pL29, presequence from Arabidopsis thaliana
-
-
?
MFRRPVLQVLRQFVRH + H2O
MFR + RPVL + QVLR + QFVRH
pSSBP, human presequence
-
-
?
additional information
?
-
-
the enzyme is active in inactivation of neuropeptides, biological relevance, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
Zn2+
zinc metallopeptidase, residues His474, His478 and Glu503 take part in the coordination of the catalytic zinc ion
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Mcc-Pro-Leu
Nln-mediated hydrolysis of QFS yields a degradation product that triggers a relatively product inhibition
additional information
Pro-Ile is unable to affect endopeptidases 24.11 and 24.15, proline endopeptidase, angiotensin-converting enzyme, leucine aminopeptidase, diglutamyl aminopeptidase, and trypsin
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
truncated enzyme NLN lacking the first 25 aa (region containing the mTP as predicted by TargetP) is not localized in the mitochondria
-
additional information
-
truncated enzyme NLN lacking the first 25 aa (region containing the mTP as predicted by TargetP) is not localized in the mitochondria
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
a network of proteases may be required for complete degradation of peptides localized in mitochondria. Mechanism of peptide binding
physiological function
neurolysin cleaves mitochondrial targeting peptides
additional information
additional information
hNLN presents a prolate ellipsoidal shape consisting of two major domains that enclose the narrow catalytic channel. The enclosed cavity structure restricts substrate length. hNLN contains the conserved HExxH zinc-binding motif, which is a signature of the MA clan of metallopeptidases. In hNLN, the residues His474, His478 and Glu503 take part in the coordination of the catalytic zinc ion. NLN structure analysis, mechanism of peptide binding, detailed overview. The large hydrophobic side chains of Ile12NT2 and Leu13NT2 may be attracted by the strong hydrophobicity of the S3' (Leu558 and Phe599) and aromatic S4' residues (Phe226, Tyr339). A single hydrogen bond between Tyr610 and Tyr11NT2 contributes to the recognition of the peptide's main chain. In addition, Arg554 (S4') offers an anchor point for the carboxyl-terminus of NT2 via salt bridge formation. Overall, peptide stabilization occurs through mainchain interactions with the observed subsites within the catalytic cavity but with these interactions not imposing a strict substrate specificity
additional information
-
hNLN presents a prolate ellipsoidal shape consisting of two major domains that enclose the narrow catalytic channel. The enclosed cavity structure restricts substrate length. hNLN contains the conserved HExxH zinc-binding motif, which is a signature of the MA clan of metallopeptidases. In hNLN, the residues His474, His478 and Glu503 take part in the coordination of the catalytic zinc ion. NLN structure analysis, mechanism of peptide binding, detailed overview. The large hydrophobic side chains of Ile12NT2 and Leu13NT2 may be attracted by the strong hydrophobicity of the S3' (Leu558 and Phe599) and aromatic S4' residues (Phe226, Tyr339). A single hydrogen bond between Tyr610 and Tyr11NT2 contributes to the recognition of the peptide's main chain. In addition, Arg554 (S4') offers an anchor point for the carboxyl-terminus of NT2 via salt bridge formation. Overall, peptide stabilization occurs through mainchain interactions with the observed subsites within the catalytic cavity but with these interactions not imposing a strict substrate specificity
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NEUL_HUMAN
704
0
80652
Swiss-Prot
Mitochondrion (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
hNLN presents a prolate ellipsoidal shape consisting of two major domains that enclose the narrow catalytic channel, NLN structure analysis, overview
additional information
-
hNLN presents a prolate ellipsoidal shape consisting of two major domains that enclose the narrow catalytic channel, NLN structure analysis, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme mutant NLNE475Q in complex with the products of neurotensin cleavage, X-ray diffraction structure determination and analysis at 2.7 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E475Q
site-directed mutagenesis, the residue Glu475 coordinates a water molecule involved in the nucleophilic attack of the scissile bond and replacing this residue with glutamine (hNLNE475Q) results in a dramatic reduction of enzyme activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene NLN, sequence comparisons and phylogenetic tree, transient transfection of HeLa cells with C-terminally myc-tagged full-length human NLN (hNLN1-704) followed by immunolocalization reveals a typical mitochondrial pattern. Transfection with a construct lacking the first 25 aa (region containing the mTP as predicted by TargetP) abolishes the mitochondrial localization of hNLN
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Vincent, B.; Vincent, J.P.; Checler, F.
Purification and characterization of human endopeptidase 3.4.24.16. Comparison with the porcine counterpart indicates a unique cleavage site on neurotensin
Brain Res.
709
51-58
1996
Homo sapiens, Sus scrofa
Krause, D.R.; Piva, T.J.; Brown, S.B.; Ellem, K.A.O.
Characterization and localization of mitochondrial oligopeptidase (MOP) (EC 3.4.24.16) activity in the human cervical adenocarcinoma cell line HeLa
J. Cell. Biochem.
66
297-308
1997
Homo sapiens
Barrett, A.J.; Dando, P.M.
Neurolysin
Handbook of Proteolytic Enzymes(Barrett,A. J. ,Rawlings,N. D. ,Woessner,J. F. ,Eds. )Academic Press
1
356-360
2004
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
-
Kitabgi, P.
Inactivation of neurotensin and neuromedin N by Zn metallopeptidases
Peptides
27
2515-2522
2006
Canis lupus familiaris, Homo sapiens, Mus musculus
Teixeira, P.F.; Masuyer, G.; Pinho, C.M.; Branca, R.M.M.; Kmiec, B.; Wallin, C.; Waermlaender, S.K.T.S.; Berntsson, R.P.; Ankarcrona, M.; Graeslund, A.; Lehtioe, J.; Stenmark, P.; Glaser, E.
Mechanism of peptide binding and cleavage by the human mitochondrial peptidase neurolysin
J. Mol. Biol.
430
348-362
2018
Homo sapiens (Q9BYT8), Homo sapiens
EXTERNAL LINKS (specific for EC-Number 3.4.24.16)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
