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Gene Review

NLE1  -  notchless homolog 1 (Drosophila)

Homo sapiens

Synonyms: FLJ10458, HUSSY-07, Notchless protein homolog 1
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Disease relevance of NLE1

  • The structure of a complex between a peptide inhibitor with the sequence N-acetyl-Thr-Ile-Nle-psi[CH2-NH]-Nle-Gln-Arg.amide (Nle, norleucine) with chemically synthesized HIV-1 (human immunodeficiency virus 1) protease was determined at 2.3 A resolution (R factor of 0.176) [1].
  • Nitrogen retention, hormone concentrations, and weight gain were measured in five bull calves (90 kg body wt) administered 0 or 0.067 microgram Nle rat hypothalamic GRF (1,29)NH2/kg body wt every 4 hr for 10 days [2].

High impact information on NLE1

  • The optimal P4 to P2 substrate specificity for plasmin was P4-Lys/Nle (norleucine)/Val/Ile/Phe, P3-Xaa, and P2-Tyr/Phe/Trp [3].
  • The granzyme H efficiently cleaved Suc-Phe-Leu-Phe-SBzl (v = 185 nM/s at [S] = 0.217 mM) and also hydrolyzed Boc-Ala-Ala-X-SBzl (X = Phe, Tyr, Met, Nle, or Nva) with slower rates but had little tryptase or Asp-ase activity [4].
  • [D-Phe6,beta-Ala11,Phe13, Nle14]Bn-(6-14) (where Nle represents norleucine) was discovered to have high potency for stimulating inositol phosphate formation in both cell lines [5].
  • Parallel cytometric and fluorimetric analyses of the interaction of a fluoresceinated N-formyl hexapeptide (N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, Nle = norleucine) with its receptors on human neutrophils are presented [6].
  • [Nle(8,18),beta-Ala(13), Nal(23),Tyr(34)]bPTH-(1-34)NH(2) (beta-hLeu = beta-homo-leucine; beta-Ala = beta-alanine; Nal = L-2-naphthyl-alanine; Nle = norleucine) [7].

Biological context of NLE1


Associations of NLE1 with chemical compounds

  • We have developed a radioiodinated photoaffinity label, N-formyl-Nle-Leu-Phe-Nle-125I-Tyr-Lys-N-6-(4'-azido-2'-nitrophenylamino) hexanoate (where Nle represents norleucine) (125I-PAL), which forms a covalent complex with the formyl peptide chemotactic receptor of living human neutrophils [11].
  • Variable-temperature NMR data in this medium show that six amide protons have low temperature coefficients, two of the five Glu's, Trp, Nle, Asp, and Phe [12].
  • Only the binding of Asn, Cys, Gln, Leu, Lys, Met, Nle, Phe, Ser, Trp and Tyr to the surfactants was observed, however, the strength of interaction was fairly low [13].
  • With alanine scanning and site-directed deletion, a typical ligand consisted of a motif of -NleDI/V/Nle- with two flanking cysteines [14].
  • Only the binding of Arg, Glu, Gly, Leu, Lys, Met, Nle, Phe Trp, Tyr and Val to the surfactant was observed, however, the strength of interaction was fairly low [15].

Other interactions of NLE1


Analytical, diagnostic and therapeutic context of NLE1

  • An optimization procedure for the separation of 24 PTH-amino acids by high-performance liquid chromatography on an inexpensive Merck Superspher Si 60 RP-8, (4.0 x 250 mm) column with PTH-Nle as an internal standard is described [17].


  1. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution. Miller, M., Schneider, J., Sathyanarayana, B.K., Toth, M.V., Marshall, G.R., Clawson, L., Selk, L., Kent, S.B., Wlodawer, A. Science (1989) [Pubmed]
  2. Growth hormone-releasing factor on growth hormone secretion in prepubertal calves. Plouzek, C.A., Vale, W., Rivier, J., Anderson, L.L., Trenkle, A. Proc. Soc. Exp. Biol. Med. (1988) [Pubmed]
  3. Synthesis of positional-scanning libraries of fluorogenic peptide substrates to define the extended substrate specificity of plasmin and thrombin. Backes, B.J., Harris, J.L., Leonetti, F., Craik, C.S., Ellman, J.A. Nat. Biotechnol. (2000) [Pubmed]
  4. The human cytotoxic T cell granule serine protease granzyme H has chymotrypsin-like (chymase) activity and is taken up into cytoplasmic vesicles reminiscent of granzyme B-containing endosomes. Edwards, K.M., Kam, C.M., Powers, J.C., Trapani, J.A. J. Biol. Chem. (1999) [Pubmed]
  5. Discovery of a high affinity radioligand for the human orphan receptor, bombesin receptor subtype 3, which demonstrates that it has a unique pharmacology compared with other mammalian bombesin receptors. Mantey, S.A., Weber, H.C., Sainz, E., Akeson, M., Ryan, R.R., Pradhan, T.K., Searles, R.P., Spindel, E.R., Battey, J.F., Coy, D.H., Jensen, R.T. J. Biol. Chem. (1997) [Pubmed]
  6. The dynamics of ligand-receptor interactions. Real-time analyses of association, dissociation, and internalization of an N-formyl peptide and its receptors on the human neutrophil. Sklar, L.A., Finney, D.A., Oades, Z.G., Jesaitis, A.J., Painter, R.G., Cochrane, C.G. J. Biol. Chem. (1984) [Pubmed]
  7. Structure-function studies of analogues of parathyroid hormone (PTH)-1-34 containing beta-amino acid residues in positions 11-13. Peggion, E., Mammi, S., Schievano, E., Silvestri, L., Schiebler, L., Bisello, A., Rosenblatt, M., Chorev, M. Biochemistry (2002) [Pubmed]
  8. Effects of urea and guanidine hydrochloride on peptide and nonpolar groups. Nandi, P.K., Robinson, D.R. Biochemistry (1984) [Pubmed]
  9. Ligand/receptor internalization: a spectroscopic analysis and a comparison of ligand binding, cellular response, and internalization by human neutrophils. Sklar, L.A., Jesaitis, A.J., Painter, R.G., Cochrane, C.G. J. Cell. Biochem. (1982) [Pubmed]
  10. Semisynthesis of Arg15, Glu15, Met15, and Nle15-aprotinin involving enzymatic peptide bond resynthesis. Beckmann, J., Mehlich, A., Schröder, W., Wenzel, H.R., Tschesche, H. J. Protein Chem. (1989) [Pubmed]
  11. Formyl peptide chemotactic receptor. Evidence for an active proteolytic fragment. Dolmatch, B., Niedel, J. J. Biol. Chem. (1983) [Pubmed]
  12. Conformational studies of human Des-Trp1,Nle12-minigastrin in water-trifluoroethanol mixtures by 1H NMR and circular dichroism. Mammi, S., Mammi, N.J., Peggion, E. Biochemistry (1988) [Pubmed]
  13. Charge-transfer chromatographic study on the interaction of amino acids with ethoxylated stearic acid surfactants. Cserháti, T. Biomed. Chromatogr. (1994) [Pubmed]
  14. Novel peptide ligands for integrin alpha 4 beta 1 overexpressed in cancer cells. Mikawa, M., Wang, H., Guo, L., Liu, R., Marik, J., Takada, Y., Lam, K., Lau, D. Mol. Cancer Ther. (2004) [Pubmed]
  15. Binding of amino acids to the cationic surfactant cetyltrimethylammoniumbromide. Cserháti, T., Forgács, E. Biochem. Mol. Biol. Int. (1995) [Pubmed]
  16. Characterization of the plant Notchless homolog, a WD repeat protein involved in seed development. Chantha, S.C., Emerald, B.S., Matton, D.P. Plant Mol. Biol. (2006) [Pubmed]
  17. An optimized procedure for the separation of amino acid phenylthiohydantoins by reversed-phase HPLC. Persson, B., Eaker, D. J. Biochem. Biophys. Methods (1990) [Pubmed]
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