1dmt
From Proteopedia
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|PDB= 1dmt |SIZE=350|CAPTION= <scene name='initialview01'>1dmt</scene>, resolution 2.1Å | |PDB= 1dmt |SIZE=350|CAPTION= <scene name='initialview01'>1dmt</scene>, resolution 2.1Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RDF:N-ALPHA-L-RHAMNOPYRANOSYLOXY(HYDROXYPHOSPHINYL)-L-LEUCYL-L-TRYPTOPHAN'>RDF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Neprilysin Neprilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.11 3.4.24.11] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Neprilysin Neprilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.11 3.4.24.11] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dmt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dmt OCA], [http://www.ebi.ac.uk/pdbsum/1dmt PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dmt RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Neutral endopeptidase is a mammalian type II integral membrane zinc-containing endopeptidase, which degrades and inactivates a number of bioactive peptides. The range of substrates cleaved by neutral endopeptidase in vitro includes the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor. Due to the physiological importance of neutral endopeptidase in the modulation of nociceptive and pressor responses there is considerable interest in inhibitors of this enzyme as novel analgesics and anti-hypertensive agents. Here we describe the crystal structure of the extracellular domain (residues 52-749) of human NEP complexed with the generic metalloproteinase inhibitor phosphoramidon at 2.1 A resolution. The structure reveals two multiply connected folding domains which embrace a large central cavity containing the active site. The inhibitor is bound to one side of this cavity and its binding mode provides a detailed understanding of the ligand-binding and specificity determinants. | Neutral endopeptidase is a mammalian type II integral membrane zinc-containing endopeptidase, which degrades and inactivates a number of bioactive peptides. The range of substrates cleaved by neutral endopeptidase in vitro includes the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor. Due to the physiological importance of neutral endopeptidase in the modulation of nociceptive and pressor responses there is considerable interest in inhibitors of this enzyme as novel analgesics and anti-hypertensive agents. Here we describe the crystal structure of the extracellular domain (residues 52-749) of human NEP complexed with the generic metalloproteinase inhibitor phosphoramidon at 2.1 A resolution. The structure reveals two multiply connected folding domains which embrace a large central cavity containing the active site. The inhibitor is bound to one side of this cavity and its binding mode provides a detailed understanding of the ligand-binding and specificity determinants. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Membranous glomerulonephritis, antenatal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120520 120520]], Neutral endopeptidase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120520 120520]], Schizophrenia, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607265 607265]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Oefner, C.]] | [[Category: Oefner, C.]] | ||
[[Category: Winkler, F K.]] | [[Category: Winkler, F K.]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: NAG]] | ||
| - | [[Category: RDF]] | ||
| - | [[Category: ZN]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
[[Category: metalloprotease]] | [[Category: metalloprotease]] | ||
[[Category: signal-anchor]] | [[Category: signal-anchor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:44:38 2008'' |
Revision as of 16:44, 30 March 2008
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| , resolution 2.1Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Neprilysin, with EC number 3.4.24.11 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF HUMAN NEUTRAL ENDOPEPTIDASE COMPLEXED WITH PHOSPHORAMIDON
Overview
Neutral endopeptidase is a mammalian type II integral membrane zinc-containing endopeptidase, which degrades and inactivates a number of bioactive peptides. The range of substrates cleaved by neutral endopeptidase in vitro includes the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor. Due to the physiological importance of neutral endopeptidase in the modulation of nociceptive and pressor responses there is considerable interest in inhibitors of this enzyme as novel analgesics and anti-hypertensive agents. Here we describe the crystal structure of the extracellular domain (residues 52-749) of human NEP complexed with the generic metalloproteinase inhibitor phosphoramidon at 2.1 A resolution. The structure reveals two multiply connected folding domains which embrace a large central cavity containing the active site. The inhibitor is bound to one side of this cavity and its binding mode provides a detailed understanding of the ligand-binding and specificity determinants.
About this Structure
1DMT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon., Oefner C, D'Arcy A, Hennig M, Winkler FK, Dale GE, J Mol Biol. 2000 Feb 18;296(2):341-9. PMID:10669592
Page seeded by OCA on Sun Mar 30 19:44:38 2008
