2bq6: Difference between revisions
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==Overview== | ==Overview== | ||
Structure-activity relationships within a series of highly potent, 2-carboxyindole-based factor Xa inhibitors incorporating a neutral P1, ligand are described with particular emphasis on the structural, requirements for addressing subpockets of the factor Xa enzyme., Interactions with the subpockets were probed by systematic substitution of, the 2-carboxyindole scaffold, in combination with privileged P1 and P4, substituents. Combining the most favorable substituents at the indole, nucleus led to the discovery of a remarkably potent factor Xa inhibitor, displaying a K(i) value of 0.07 nM. X-ray crystallography of inhibitors, bound to factor Xa revealed substituent-dependent switching of the, inhibitor binding mode and provided a rationale for the SAR obtained., These results underscore . | Structure-activity relationships within a series of highly potent, 2-carboxyindole-based factor Xa inhibitors incorporating a neutral P1, ligand are described with particular emphasis on the structural, requirements for addressing subpockets of the factor Xa enzyme., Interactions with the subpockets were probed by systematic substitution of, the 2-carboxyindole scaffold, in combination with privileged P1 and P4, substituents. Combining the most favorable substituents at the indole, nucleus led to the discovery of a remarkably potent factor Xa inhibitor, displaying a K(i) value of 0.07 nM. X-ray crystallography of inhibitors, bound to factor Xa revealed substituent-dependent switching of the, inhibitor binding mode and provided a rationale for the SAR obtained., These results underscore the key role played by the P1 ligand not only in, determining the binding affinity of the inhibitor by direct interaction, but also in modifying the binding mode of the whole scaffold, resulting in, a nonlinear SAR. | ||
==About this Structure== | ==About this Structure== | ||
2BQ6 is a | 2BQ6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and IIB as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BQ6 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:22:10 2007'' | ||
