 |
PDBsum entry 1b0f
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Hydrolase
|
|
|
Title:
|
|
Crystal structure of human neutrophil elastase with mdl 101, 146
|
|
Structure:
|
|
Protein (elastase). Chain: a. Synonym: hne. Ec: 3.4.21.37
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Cell: neutrophil
|
|
Resolution:
|
|
|
|
Authors:
|
|
H.A.Schreuder,W.A.Metz,N.P.Peet,J.T.Pelton,C.Tardif
|
|
Key ref:
|
|
R.J.Cregge
et al.
(1998).
Inhibition of human neutrophil elastase. 4. Design, synthesis, X-ray crystallographic analysis, and structure-activity relationships for a series of P2-modified, orally active peptidyl pentafluoroethyl ketones.
J Med Chem,
41,
2461-2480.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
09-Nov-98
|
Release date:
|
09-Nov-98
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P08246
(ELNE_HUMAN) -
Neutrophil elastase from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
267 a.a.
218 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.3.4.21.37
- leukocyte elastase.
|
|
|
|
|
|
|
Reaction:
|
|
Hydrolysis of proteins, including elastin. Preferential cleavage: Val-|-Xaa > Ala-|-Xaa.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
J Med Chem
41:2461-2480
(1998)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Inhibition of human neutrophil elastase. 4. Design, synthesis, X-ray crystallographic analysis, and structure-activity relationships for a series of P2-modified, orally active peptidyl pentafluoroethyl ketones.
|
|
R.J.Cregge,
S.L.Durham,
R.A.Farr,
S.L.Gallion,
C.M.Hare,
R.V.Hoffman,
M.J.Janusz,
H.O.Kim,
J.R.Koehl,
S.Mehdi,
W.A.Metz,
N.P.Peet,
J.T.Pelton,
H.A.Schreuder,
S.Sunder,
C.Tardif.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
A series of P2-modified, orally active peptidic inhibitors of human neutrophil
elastase (HNE) are reported. These pentafluoroethyl ketone-based inhibitors were
designed using pentafluoroethyl ketone 1 as a model. Rational structural
modifications were made at the P3, P2, and activating group (AG) portions of 1
based on structure-activity relationships (SAR) developed from in vitro
(measured Ki) data and information provided by modeling studies that docked
inhibitor 1 into the active site of HNE. The modeling-based design was
corroborated with X-ray crystallographic analysis of the complex between 1 and
porcine pancreatic elastase (PPE) and subsequently the complex between 1 and HNE.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
X.Q.Yu,
T.Shirai,
Y.Yamamoto,
and
N.Miyaura
(2011).
Rhodium-Catalyzed 1,4-Addition of Lithium 2-Furyltriolborates to Unsaturated Ketones and Esters for Enantioselective Synthesis of γ-Oxo-Carboxylic Acids By Oxidation of the Furyl Ring with Ozone.
|
| |
Chem Asian J,
6,
932-937.
|
|
|
|
|
|
|
E.Hajjar,
T.Broemstrup,
C.Kantari,
V.Witko-Sarsat,
and
N.Reuter
(2010).
Structures of human proteinase 3 and neutrophil elastase--so similar yet so different.
|
| |
FEBS J,
277,
2238-2254.
|
|
|
|
|
|
|
M.Yashiro,
Y.Kawakami,
J.Taya,
S.Arai,
and
Y.Fujii
(2009).
Zn(II) complex for selective and rapid scission of protein backbone.
|
| |
Chem Commun (Camb),
(),
1544-1546.
|
|
|
|
|
|
|
M.Koizumi,
A.Fujino,
K.Fukushima,
T.Kamimura,
and
M.Takimoto-Kamimura
(2008).
Complex of human neutrophil elastase with 1/2SLPI.
|
| |
J Synchrotron Radiat,
15,
308-311.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
G.Li,
and
W.A.van der Donk
(2007).
Efficient synthesis of suitably protected beta-difluoroalanine and gamma-difluorothreonine from L-ascorbic acid.
|
| |
Org Lett,
9,
41-44.
|
|
|
|
|
|
|
D.L.Boger,
H.Sato,
A.E.Lerner,
M.P.Hedrick,
R.A.Fecik,
H.Miyauchi,
G.D.Wilkie,
B.J.Austin,
M.P.Patricelli,
and
B.F.Cravatt
(2000).
Exceptionally potent inhibitors of fatty acid amide hydrolase: the enzyme responsible for degradation of endogenous oleamide and anandamide.
|
| |
Proc Natl Acad Sci U S A,
97,
5044-5049.
|
|
|
|
|
|
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
code is
shown on the right.
|
|
Links
