 |
PDBsum entry 2zzu
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/blood clotting
|
PDB id
|
|
|
|
2zzu
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
142 a.a.
|
|
|
|
|
|
|
|
|
|
|
254 a.a.
|
|
|
|
|
|
|
|
|
|
|
191 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Hydrolase/blood clotting
|
|
|
Title:
|
|
Human factor viia-tissue factor complexed with ethylsulfonamide-d-5- (3-carboxybenzyloxy)-trp-gln-p-aminobenzamidine
|
|
Structure:
|
|
Factor vii light chain. Chain: l. Fragment: unp residues 61-212. Synonym: serum prothrombin conversion accelerator, spca, proconvertin. Engineered: yes. Factor vii heavy chain. Chain: h. Fragment: unp residues 213-466.
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: f7. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: cho. Gene: f3. Expressed in: escherichia coli.
|
|
Resolution:
|
|
|
2.50Å
|
R-factor:
|
0.221
|
R-free:
|
0.273
|
|
|
Authors:
|
|
S.Kadono,A.Sakamoto,Y.Kikuchi,M.Oh-Eda,N.Yabuta,T.Koga,K.Hattori, T.Shiraishi,M.Haramura,H.Sato,M.Ohta,T.Kozono
|
|
Key ref:
|
|
T.Shiraishi
et al.
(2010).
Design and synthesis of peptidomimetic factor VIIa inhibitors.
Chem Pharm Bull (tokyo),
58,
38-44.
PubMed id:
|
|
|
Date:
|
|
|
25-Feb-09
|
Release date:
|
24-Mar-09
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P08709
(FA7_HUMAN) -
Coagulation factor VII from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
466 a.a.
142 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
Chains L, H:
E.C.3.4.21.21
- coagulation factor VIIa.
|
|
|
|
|
|
|
Reaction:
|
|
Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Chem Pharm Bull (tokyo)
58:38-44
(2010)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Design and synthesis of peptidomimetic factor VIIa inhibitors.
|
|
T.Shiraishi,
S.Kadono,
M.Haramura,
H.Kodama,
Y.Ono,
H.Iikura,
T.Esaki,
T.Koga,
K.Hattori,
Y.Watanabe,
A.Sakamoto,
K.Yoshihashi,
T.Kitazawa,
K.Esaki,
M.Ohta,
H.Sato,
T.Kozono.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as
a promising target for developing new anticoagulant drugs. In previous reports,
we described a S3 subsite found in the X-ray crystal structure of compound 2
that bound to FVIIa/soluble tissue factor (sTF). Based on the X-ray crystal
structure information and with the aim of improving the inhibition activity for
FVIIa/TF and selectivity against other serine proteases, we synthesized
derivatives by introducing substituents at position 5 of the indole ring of
compound 2. Among them, compound 16 showed high selectivity against other serine
proteases. Contrary to our expectations, compound 16 did not occupy the
S3-subsite; X-ray structure analysis revealed that compound 16 improved
selectivity by forming hydrogen bonds with Gln217, Thr99 and Asn100.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
| |
Links
