Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.21.6 (
thromboplastin
)
13,278
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Factor Xa, the converting enzyme of prothrombin to thrombin, has emerged as an alternative (to thrombin) target for drug discovery for thromboembolic diseases. An inhibitor has been synthesized and the crystal structure of the complex between Des[1-44]
factor Xa
and the inhibitor has been determined by crystallographic methods in two different crystal forms to 2.3- and 2.4-A resolution. The racemic mixture of inhibitor FX-2212, (2RS)-(3'-amidino-3-biphenylyl)-5-(4-pyridylamino)
pentanoic acid
, inhibits
factor Xa
activity by 50% at 272 nM in vitro. The S-isomer of FX-2212 (FX-2212a) was found to bind to the active site of
factor Xa
in both crystal forms. The biphenylamidine of FX-2212a occupies the S1-pocket, and the pyridine ring makes hydrophobic interactions with the
factor Xa
aryl-binding site. Several water molecules meditate inhibitor binding to residues in the active site. In contrast to the earlier crystal structures of
factor Xa
, such as those of apo-Des[1-45]
factor Xa
and Des[1-44]
factor Xa
in complex with a naphthyl inhibitor DX-9065a, two epidermal growth factor-like domains of
factor Xa
are well ordered in both our crystal forms as well as the region between the two domains, which recently was found to be the binding site of the effector cell protease receptor-1. This structure provides a basis for designing next generation inhibitors of
factor Xa
.
...
PMID:Structural basis for chemical inhibition of human blood coagulation factor Xa. 961 63
