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Literature summary for 3.4.24.16 extracted from

  • 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 (2018), J. Mol. Biol., 430, 348-362 .
    View publication on PubMed
Search for more literature for 3.4.24.16

Cloned(Commentary)

Cloned (Comment) Organism
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 Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
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 Homo sapiens

Protein Variants

Protein Variants Comment Organism
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 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion tagged full-length NLN (hNLN1-704) Homo sapiens 5739
-
mitoplast
-
 Homo sapiens
-
-
additional information truncated enzyme NLN lacking the first 25 aa (region containing the mTP as predicted by TargetP) is not localized in the mitochondria Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Zn2+ zinc metallopeptidase, residues His474, His478 and Glu503 take part in the coordination of the catalytic zinc ion Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
amyloid-beta35-40 + H2O Homo sapiens
-
 ?
-
 ?
FSTSAQNN + H2O Homo sapiens octMdh1, Oct1 generated octapeptide from Mus musculus ?
-
 ?
GlpLYENKPRRPYIL + H2O Homo sapiens neurotensin, secreted human neuropeptide GlpLYENKPRRP + YIL
-
 ?
MFLTRFVGRRFLAAASARS + H2O Homo sapiens pL29, presequence from Arabidopsis thaliana MFLTR + FVG + RRFL + 2 L-Ala + ASA + RS
-
 ?
MFRRPVLQVLRQFVRH + H2O Homo sapiens pSSBP, human presequence MFR + RPVL + QVLR + QFVRH
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9BYT8
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
 Homo sapiens
-
gastrointestinal tract
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
amyloid-beta35-40 + H2O
-
 Homo sapiens ?
-
 ?
FSTSAQNN + H2O octMdh1, Oct1 generated octapeptide from Mus musculus Homo sapiens ?
-
 ?
GlpLYENKPRRPYIL + H2O neurotensin, secreted human neuropeptide Homo sapiens GlpLYENKPRRP + YIL
-
 ?
MFLTRFVGRRFLAAASARS + H2O pL29, presequence from Arabidopsis thaliana Homo sapiens MFLTR + FVG + RRFL + 2 L-Ala + ASA + RS
-
 ?
MFRRPVLQVLRQFVRH + H2O pSSBP, human presequence Homo sapiens MFR + RPVL + QVLR + QFVRH
-
 ?
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 Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
More hNLN presents a prolate ellipsoidal shape consisting of two major domains that enclose the narrow catalytic channel, NLN structure analysis, overview Homo sapiens

Synonyms

Synonyms Comment Organism
mitochondrial peptidase
-
 Homo sapiens
Nln
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8.2
-
 assay at Homo sapiens

General Information

General Information Comment Organism
metabolism a network of proteases may be required for complete degradation of peptides localized in mitochondria. Mechanism of peptide binding Homo sapiens
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 Homo sapiens
physiological function neurolysin cleaves mitochondrial targeting peptides Homo sapiens