1v3x: Difference between revisions
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'''Factor Xa in complex with the inhibitor 1-[6-methyl-4,5,6,7-tetrahydrothiazolo(5,4-c)pyridin-2-yl] carbonyl-2-carbamoyl-4-(6-chloronaphth-2-ylsulphonyl)piperazine''' | {{Structure | ||
|PDB= 1v3x |SIZE=350|CAPTION= <scene name='initialview01'>1v3x</scene>, resolution 2.20Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=D76:(2R)-4-[(6-CHLORO-2-NAPHTHYL)SULFONYL]-1-[(5-METHYL-4,5,6,7-TETRAHYDRO[1,3]THIAZOLO[5,4-C]PYRIDIN-2-YL)CARBONYL]PIPERAZINE-2-CARBOXAMIDE'>D76</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] | |||
|GENE= | |||
}} | |||
'''Factor Xa in complex with the inhibitor 1-[6-methyl-4,5,6,7-tetrahydrothiazolo(5,4-c)pyridin-2-yl] carbonyl-2-carbamoyl-4-(6-chloronaphth-2-ylsulphonyl)piperazine''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1V3X is a [ | 1V3X is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V3X OCA]. | ||
==Reference== | ==Reference== | ||
Synthesis and conformational analysis of a non-amidine factor Xa inhibitor that incorporates 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 binding element., Haginoya N, Kobayashi S, Komoriya S, Yoshino T, Suzuki M, Shimada T, Watanabe K, Hirokawa Y, Furugori T, Nagahara T, J Med Chem. 2004 Oct 7;47(21):5167-82. PMID:[http:// | Synthesis and conformational analysis of a non-amidine factor Xa inhibitor that incorporates 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 binding element., Haginoya N, Kobayashi S, Komoriya S, Yoshino T, Suzuki M, Shimada T, Watanabe K, Hirokawa Y, Furugori T, Nagahara T, J Med Chem. 2004 Oct 7;47(21):5167-82. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15456260 15456260] | ||
[[Category: Coagulation factor Xa]] | [[Category: Coagulation factor Xa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:40:31 2008'' | ||
Revision as of 15:40, 20 March 2008
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| , resolution 2.20Å | |||||||
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| Ligands: | and | ||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Factor Xa in complex with the inhibitor 1-[6-methyl-4,5,6,7-tetrahydrothiazolo(5,4-c)pyridin-2-yl] carbonyl-2-carbamoyl-4-(6-chloronaphth-2-ylsulphonyl)piperazine
OverviewOverview
Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.
DiseaseDisease
Known disease associated with this structure: Factor X deficiency OMIM:[227600]
About this StructureAbout this Structure
1V3X is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Synthesis and conformational analysis of a non-amidine factor Xa inhibitor that incorporates 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 binding element., Haginoya N, Kobayashi S, Komoriya S, Yoshino T, Suzuki M, Shimada T, Watanabe K, Hirokawa Y, Furugori T, Nagahara T, J Med Chem. 2004 Oct 7;47(21):5167-82. PMID:15456260
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