2Y5F: FACTOR XA - CATION INHIBITOR COMPLEX

Citation:
Abstract
Factor Xa, a serine protease from the blood coagulation cascade, is an ideal enzyme for molecular recognition studies, as its active site is highly shape-persistent and features distinct, concave sub-pockets. We developed a family of non-peptidic, small-molecule inhibitors with a central tricyclic core orienting a neutral heterocyclic substituent into the S1 pocket and a quaternary ammonium ion into the aromatic box in the S4 pocket. The substituents were systematically varied to investigate cation-pi interactions in the S4 pocket, optimal heterocyclic stacking on the flat peptide walls lining the S1 pocket, and potential water replacements in both the S1 and the S4 pockets. Structure-activity relationships were established to reveal and quantify contributions to the binding free enthalpy, resulting from single-atom replacements or positional changes in the ligands. A series of high-affinity ligands with inhibitory constants down to K(i)=2 nM were obtained and their proposed binding geometries confirmed by X-ray co-crystal structures of protein-ligand complexes.
PDB ID: 2Y5FDownload
MMDB ID: 96003
PDB Deposition Date: 2011/1/13
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 1.29  Å
Source Organism:
Similar Structures:
Biological Unit for 2Y5F: dimeric; determined by author and by software (PISA)
Molecular Components in 2Y5F
Label Count Molecule
Proteins (2 molecules)
1
Activated Factor XA Heavy Chain(Gene symbol: F10)
Molecule annotation
1
Factor X Light Chain(Gene symbol: F10)
Molecule annotation
Chemicals (3 molecules)
1
1
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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