1kye
From Proteopedia
(New page: 200px<br /> <applet load="1kye" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kye, resolution 2.22Å" /> '''Factor Xa in comple...) |
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| - | [[Image:1kye.gif|left|200px]]<br /> | + | [[Image:1kye.gif|left|200px]]<br /><applet load="1kye" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1kye" size=" | + | |
caption="1kye, resolution 2.22Å" /> | caption="1kye, resolution 2.22Å" /> | ||
'''Factor Xa in complex with (R)-2-(3-adamantan-1-yl-ureido)-3-(3-carbamimidoyl-phenyl)-N-phenethyl-propionamide'''<br /> | '''Factor Xa in complex with (R)-2-(3-adamantan-1-yl-ureido)-3-(3-carbamimidoyl-phenyl)-N-phenethyl-propionamide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A putative non-substrate like binding mode of (R)-3-amidinophenylalanine | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1KYE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and RUP 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] Full crystallographic information is available from [http:// | + | 1KYE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=RUP:'>RUP</scene> 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KYE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bode, W.]] | [[Category: Bode, W.]] | ||
[[Category: Moroder, L.]] | [[Category: Moroder, L.]] | ||
| - | [[Category: Mueller, M | + | [[Category: Mueller, M M.]] |
[[Category: Sperl, S.]] | [[Category: Sperl, S.]] | ||
[[Category: Sturzebecher, J.]] | [[Category: Sturzebecher, J.]] | ||
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[[Category: factor xa]] | [[Category: factor xa]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:39:18 2008'' |
Revision as of 11:39, 21 February 2008
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Factor Xa in complex with (R)-2-(3-adamantan-1-yl-ureido)-3-(3-carbamimidoyl-phenyl)-N-phenethyl-propionamide
Contents |
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.
Disease
Known disease associated with this structure: Factor X deficiency OMIM:[227600]
About this Structure
1KYE is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Coagulation factor Xa, with EC number 3.4.21.6 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
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