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PDBsum entry 1r1h
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural analysis of neprilysin with various specific and potent inhibitors.
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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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Ref.
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Acta Crystallogr D Biol Crystallogr, 2004,
60,
392-396.
[DOI no: ]
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PubMed id
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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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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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