2ZZU: Human Factor Viia-Tissue Factor Complexed With Ethylsulfonamide-D-5- (3-Carboxybenzyloxy)-Trp-Gln-P-Aminobenzamidine

Citation:
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.
PDB ID: 2ZZUDownload
MMDB ID: 70357
PDB Deposition Date: 2009/2/25
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Similar Structures:
Biological Unit for 2ZZU: trimeric; determined by author and by software (PISA)
Molecular Components in 2ZZU
Label Count Molecule
Proteins (3 molecules)
1
Factor VII Light Chain(Gene symbol: F7)
Molecule annotation
1
Factor VII Heavy Chain(Gene symbol: F7)
Molecule annotation
1
Tissue Factor(Gene symbol: F3)
Molecule annotation
Chemicals (12 molecules)
1
1
2
1
3
9
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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