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PDBsum entry 1r1i
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Structural analysis of neprilysin with various specific and potent inhibitors
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Structure:
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Neprilysin. Chain: a. Fragment: extracellular domain (residue 54-749). Synonym: neutral endopeptidase, nep, enkephalinase, common acute lymphocytic leukemia antigen, calla, neutral endopeptidase 24.11, cd10. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: mme or epn. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.
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Resolution:
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2.60Å
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R-factor:
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0.280
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R-free:
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0.358
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Authors:
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C.Oefner,B.P.Roques,M.C.Fournie-Zaluski,G.E.Dale
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Key ref:
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C.Oefner
et al.
(2004).
Structural analysis of neprilysin with various specific and potent inhibitors.
Acta Crystallogr D Biol Crystallogr,
60,
392-396.
PubMed id:
DOI:
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Date:
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24-Sep-03
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Release date:
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28-Sep-04
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PROCHECK
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Headers
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References
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P08473
(NEP_HUMAN) -
Neprilysin from Homo sapiens
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Seq:
Struc:
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750 a.a.
696 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.4.24.11
- neprilysin.
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Reaction:
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Preferential cleavage at the amino group of hydrophobic residues in insulin, casein, hemoglobin, and a number of other proteins and polypeptides.
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Cofactor:
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Zn(2+)
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DOI no:
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Acta Crystallogr D Biol Crystallogr
60:392-396
(2004)
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PubMed id:
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Structural analysis of neprilysin with various specific and potent inhibitors.
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C.Oefner,
B.P.Roques,
M.C.Fournie-Zaluski,
G.E.Dale.
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ABSTRACT
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Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic
inactivation of a number of bioactive peptides including the enkephalins,
substance P, endothelin, bradykinin and atrial natriuretic factor. Owing to the
physiological importance of NEP in the modulation of nociceptive and pressor
responses, there is considerable interest in inhibitors of this enzyme as novel
analgesics and antihypertensive agents. Here, the crystal structures of the
soluble extracellular domain of human NEP (residues 52-749) complexed with
various potent and competitive inhibitors are described. The structures
unambiguously reveal the binding mode of the different zinc-chelating groups and
the subsite specificity of the enzyme.
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Selected figure(s)
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Figure 3.
Figure 3 Binding modes of compounds (1), (2) and (3) to the
active site of human sNEP. Intermolecular hydrogen bonds are
indicated by dashed lines.
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The above figure is
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2004,
60,
392-396)
copyright 2004.
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Figure was
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.Perez-Andres,
B.Paiva,
W.G.Nieto,
A.Caraux,
A.Schmitz,
J.Almeida,
R.F.Vogt,
G.E.Marti,
A.C.Rawstron,
M.C.Van Zelm,
J.J.Van Dongen,
H.E.Johnsen,
B.Klein,
and
A.Orfao
(2010).
Human peripheral blood B-cell compartments: a crossroad in B-cell traffic.
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Cytometry B Clin Cytom,
78,
S47-S60.
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N.K.Rao,
A.Yadav,
and
S.Kumar Singh
(2009).
An ab initio quantum mechanical drug designing procedure: application to the design of balanced dual ACE/NEP inhibitors.
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J Mol Model,
15,
1447-1462.
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E.Malito,
R.E.Hulse,
and
W.J.Tang
(2008).
Amyloid beta-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin.
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Cell Mol Life Sci,
65,
2574-2585.
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E.J.Lim,
S.Sampath,
J.Coll-Rodriguez,
J.Schmidt,
K.Ray,
and
D.W.Rodgers
(2007).
Swapping the substrate specificities of the neuropeptidases neurolysin and thimet oligopeptidase.
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J Biol Chem,
282,
9722-9732.
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PDB codes:
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O.Raguin,
M.C.Fournié-Zaluski,
A.Romieu,
A.Pèlegrin,
F.Chatelet,
D.Pélaprat,
J.Barbet,
B.P.Roques,
and
A.Gruaz-Guyon
(2005).
A labeled neutral endopeptidase inhibitor as a potential tool for tumor diagnosis and prognosis.
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Angew Chem Int Ed Engl,
44,
4058-4061.
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S.Voisin,
D.Rognan,
C.Gros,
and
T.Ouimet
(2004).
A three-dimensional model of the neprilysin 2 active site based on the X-ray structure of neprilysin. Identification of residues involved in substrate hydrolysis and inhibitor binding of neprilysin 2.
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J Biol Chem,
279,
46172-46181.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
