This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
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...) |
|||
| Line 1: | Line 1: | ||
| - | [[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== | ||
| Line 11: | Line 10: | ||
==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== | ||
| Line 20: | Line 19: | ||
[[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.]] | ||
| Line 28: | Line 27: | ||
[[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
|
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
Page seeded by OCA on Thu Feb 21 13:39:18 2008
