 |
PDBsum entry 1jwt
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Hydrolase
|
|
|
Title:
|
|
Crystal structure of thrombin in complex with a novel bicyclic lactam inhibitor
|
|
Structure:
|
|
Prothrombin. Chain: a. Fragment: residues 328-622. Synonym: coagulation factor ii. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606
|
|
Resolution:
|
|
|
2.50Å
|
R-factor:
|
0.182
|
R-free:
|
0.301
|
|
|
Authors:
|
|
S.Levesque,Y.St-Denis,B.Bachand,P.Preville,L.Leblond,P.D.Winocour, J.J.Edmunds,J.R.Rubin,M.A.Siddiqui
|
|
Key ref:
|
|
S.Lévesque
et al.
(2001).
Novel bicyclic lactam inhibitors of thrombin: potency and selectivity optimization through P1 residues.
Bioorg Med Chem Lett,
11,
3161-3164.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
05-Sep-01
|
Release date:
|
27-Feb-02
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P00734
(THRB_HUMAN) -
Prothrombin from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
622 a.a.
299 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.3.4.21.5
- thrombin.
|
|
|
|
|
|
|
Reaction:
|
|
Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Bioorg Med Chem Lett
11:3161-3164
(2001)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Novel bicyclic lactam inhibitors of thrombin: potency and selectivity optimization through P1 residues.
|
|
S.Lévesque,
Y.St-Denis,
B.Bachand,
P.Préville,
L.Leblond,
P.D.Winocour,
J.J.Edmunds,
J.R.Rubin,
M.A.Siddiqui.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Peptidomimetic inhibitors of thrombin lacking the important Ser195-carbonyl
interaction have been prepared. The binding energy lost after the removal of the
activated carbonyl was recaptured through a series of modifications of the P1
residues of the bicyclic lactam inhibitors. Selected substituted compounds
displayed useful pharmacological profiles both in vitro and in vivo.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
D.Blomberg,
T.Fex,
Y.Xue,
K.Brickmann,
and
J.Kihlberg
(2007).
Design, synthesis and biological evaluation of thrombin inhibitors based on a pyridine scaffold.
|
| |
Org Biomol Chem,
5,
2599-2605.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
S.Srivastava,
L.N.Goswami,
and
D.K.Dikshit
(2005).
Progress in the design of low molecular weight thrombin inhibitors.
|
| |
Med Res Rev,
25,
66-92.
|
|
|
|
|
|
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
