2q1j
From Proteopedia
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|PDB= 2q1j |SIZE=350|CAPTION= <scene name='initialview01'>2q1j</scene>, resolution 1.90Å | |PDB= 2q1j |SIZE=350|CAPTION= <scene name='initialview01'>2q1j</scene>, resolution 1.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FXI:1-(BUTYL{[(4-CHLOROPHENYL)AMINO]CARBONYL}AMINO)-N-[3-FLUORO-2'-(METHYLSULFONYL)BIPHENYL-4-YL]CYCLOPROPANECARBOXAMIDE'>FXI</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q1j OCA], [http://www.ebi.ac.uk/pdbsum/2q1j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2q1j RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Herein, we report on the identification of three potent glycine and related amino acid-based series of FXa inhibitors containing a neutral P1 chlorophenyl pharmacophore. A X-ray crystal structure has shown that constrained glycine derivatives with optimized N-substitution can greatly increase hydrophobic interactions in the FXa active site. Also, the substitution of a pyridone ring for a phenylsulfone ring in the P4 sidechain resulted in an inhibitor with enhanced oral bioavailability. | Herein, we report on the identification of three potent glycine and related amino acid-based series of FXa inhibitors containing a neutral P1 chlorophenyl pharmacophore. A X-ray crystal structure has shown that constrained glycine derivatives with optimized N-substitution can greatly increase hydrophobic interactions in the FXa active site. Also, the substitution of a pyridone ring for a phenylsulfone ring in the P4 sidechain resulted in an inhibitor with enhanced oral bioavailability. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Kohrt, J T.]] | [[Category: Kohrt, J T.]] | ||
[[Category: Zhang, E.]] | [[Category: Zhang, E.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: FXI]] | ||
[[Category: blood coagulation]] | [[Category: blood coagulation]] | ||
[[Category: calcium]] | [[Category: calcium]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:43:23 2008'' |
Revision as of 01:43, 31 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The discovery of glycine and related amino acid-based factor xa inhibitors
Overview
Herein, we report on the identification of three potent glycine and related amino acid-based series of FXa inhibitors containing a neutral P1 chlorophenyl pharmacophore. A X-ray crystal structure has shown that constrained glycine derivatives with optimized N-substitution can greatly increase hydrophobic interactions in the FXa active site. Also, the substitution of a pyridone ring for a phenylsulfone ring in the P4 sidechain resulted in an inhibitor with enhanced oral bioavailability.
About this Structure
2Q1J is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The discovery of glycine and related amino acid-based factor Xa inhibitors., Kohrt JT, Filipski KJ, Cody WL, Bigge CF, La F, Welch K, Dahring T, Bryant JW, Leonard D, Bolton G, Narasimhan L, Zhang E, Peterson JT, Haarer S, Sahasrabudhe V, Janiczek N, Desiraju S, Hena M, Fiakpui C, Saraswat N, Sharma R, Sun S, Maiti SN, Leadley R, Edmunds JJ, Bioorg Med Chem. 2006 Jul 1;14(13):4379-92. Epub 2006 Mar 10. PMID:16529937
Page seeded by OCA on Mon Mar 31 04:43:23 2008
Categories: Coagulation factor Xa | Homo sapiens | Protein complex | Bigge, C F. | Cody, W L. | Filipski, K J. | Finzel, B C. | Kohrt, J T. | Zhang, E. | Blood coagulation | Calcium | Cleavage on pair of basic residue | Coagulation fxa | Egf-like domain | Gamma-carboxyglutamic acid | Glycoprotein | Hydrolase | Hydroxylation | Polymorphism | Protease | Serine protease | Zymogen
