1kye
From Proteopedia
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|PDB= 1kye |SIZE=350|CAPTION= <scene name='initialview01'>1kye</scene>, resolution 2.22Å | |PDB= 1kye |SIZE=350|CAPTION= <scene name='initialview01'>1kye</scene>, resolution 2.22Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=RUP:(R)-2-(3-ADAMANTAN-1-YL-UREIDO)-3-(3-CARBAMIMIDOYL-PHENYL)-N-PHENETHYL-PROPIONAMIDE'>RUP</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=[[1fax|1FAX]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kye OCA], [http://www.ebi.ac.uk/pdbsum/1kye PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1kye RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
A putative non-substrate like binding mode of (R)-3-amidinophenylalanine derivatives to factor Xa, as derived from modeling experiments based on X-ray analysis of their complexes with trypsin, was used to design a new generation of inhibitors. However, the resulting inhibitory potencies were not at all consistent with the working assumption, although with an adamantyl-ureido derivative of (R)-3-amidinophenylalanine phenetyl amide a highly selective nanomolar inhibition of factor Xa was achieved. The X-ray analysis of the complex of this ligand with factor Xa revealed an unexpected new binding mode, of which the most important feature is the interaction of the C-terminal aryl moiety with a hydrophobic subregion of the S1 subsite, while the adamantyl group occupies the hydrophobic S3/S4 subsites of the enzyme. | A putative non-substrate like binding mode of (R)-3-amidinophenylalanine derivatives to factor Xa, as derived from modeling experiments based on X-ray analysis of their complexes with trypsin, was used to design a new generation of inhibitors. However, the resulting inhibitory potencies were not at all consistent with the working assumption, although with an adamantyl-ureido derivative of (R)-3-amidinophenylalanine phenetyl amide a highly selective nanomolar inhibition of factor Xa was achieved. The X-ray analysis of the complex of this ligand with factor Xa revealed an unexpected new binding mode, of which the most important feature is the interaction of the C-terminal aryl moiety with a hydrophobic subregion of the S1 subsite, while the adamantyl group occupies the hydrophobic S3/S4 subsites of the enzyme. | ||
| - | |||
| - | ==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: Sperl, S.]] | [[Category: Sperl, S.]] | ||
[[Category: Sturzebecher, J.]] | [[Category: Sturzebecher, J.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: RUP]] | ||
[[Category: coagulation factor inhibitor]] | [[Category: coagulation factor inhibitor]] | ||
[[Category: factor xa]] | [[Category: factor xa]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:55:23 2008'' |
Revision as of 18:55, 30 March 2008
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| , resolution 2.22Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||
| Related: | 1FAX
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Factor Xa in complex with (R)-2-(3-adamantan-1-yl-ureido)-3-(3-carbamimidoyl-phenyl)-N-phenethyl-propionamide
Overview
A putative non-substrate like binding mode of (R)-3-amidinophenylalanine derivatives to factor Xa, as derived from modeling experiments based on X-ray analysis of their complexes with trypsin, was used to design a new generation of inhibitors. However, the resulting inhibitory potencies were not at all consistent with the working assumption, although with an adamantyl-ureido derivative of (R)-3-amidinophenylalanine phenetyl amide a highly selective nanomolar inhibition of factor Xa was achieved. The X-ray analysis of the complex of this ligand with factor Xa revealed an unexpected new binding mode, of which the most important feature is the interaction of the C-terminal aryl moiety with a hydrophobic subregion of the S1 subsite, while the adamantyl group occupies the hydrophobic S3/S4 subsites of the enzyme.
About this Structure
1KYE is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
(R)-3-Amidinophenylalanine-derived inhibitors of factor Xa with a novel active-site binding mode., Mueller MM, Sperl S, Sturzebecher J, Bode W, Moroder L, Biol Chem. 2002 Jul-Aug;383(7-8):1185-91. PMID:12437104
Page seeded by OCA on Sun Mar 30 21:55:23 2008
