 |
PDBsum entry 1kye
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
(R)-3-Amidinophenylalanine-Derived inhibitors of factor xa with a novel active-Site binding mode.
|
|
|
Authors
|
|
M.M.Mueller,
S.Sperl,
J.Stürzebecher,
W.Bode,
L.Moroder.
|
|
|
Ref.
|
|
Biol Chem, 2002,
383,
1185-1191.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
A putative non-substrate like binding mode of (R)-3-amidinophenylalanine
derivatives to factor Xa, as derived from modeling experiments based on X-ray
analysis of their complexes with trypsin, was used to design a new generation of
inhibitors. However, the resulting inhibitory potencies were not at all
consistent with the working assumption, although with an adamantyl-ureido
derivative of (R)-3-amidinophenylalanine phenetyl amide a highly selective
nanomolar inhibition of factor Xa was achieved. The X-ray analysis of the
complex of this ligand with factor Xa revealed an unexpected new binding mode,
of which the most important feature is the interaction of the C-terminal aryl
moiety with a hydrophobic subregion of the S1 subsite, while the adamantyl group
occupies the hydrophobic S3/S4 subsites of the enzyme.
|
|
|
|
|
|
|
