1fv9
From Proteopedia
(New page: 200px<br /> <applet load="1fv9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fv9, resolution 3.00Å" /> '''Crystal structure o...) |
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| - | [[Image:1fv9.gif|left|200px]]<br /> | + | [[Image:1fv9.gif|left|200px]]<br /><applet load="1fv9" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1fv9" size=" | + | |
caption="1fv9, resolution 3.00Å" /> | caption="1fv9, resolution 3.00Å" /> | ||
'''Crystal structure of human microurokinase in complex with 2-amino-5-hydroxy-benzimidazole'''<br /> | '''Crystal structure of human microurokinase in complex with 2-amino-5-hydroxy-benzimidazole'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Using an NMR-based screen, a novel class of urokinase inhibitors were | + | Using an NMR-based screen, a novel class of urokinase inhibitors were identified that contain a 2-aminobenzimidazole moiety. The inhibitory potency of this family of inhibitors is similar to that of inhibitors containing a guanidine or amidine group. However, unlike previously described guanidino- or amidino-based inhibitors which have pK(a) values greater than 9.0, urokinase inhibitors containing a 2-aminobenzimidazole have pK(a) values of 7.5. Thus, 2-aminobenzimidazoles may have improved pharmacokinetic properties which could increase the bioavailability of inhibitors which contain this moiety. A crystal structure of one of the lead inhibitors, 2-amino-5-hydroxybenzimidazole, complexed with urokinase reveals the electrostatic and hydrophobic interactions that stabilize complex formation and suggests nearby subsites that may be accessed to increase the potency of this new series of urokinase inhibitors. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1FV9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and 172 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] Full crystallographic information is available from [http:// | + | 1FV9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=172:'>172</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FV9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: plasminogen activation]] | [[Category: plasminogen activation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:42:58 2008'' |
Revision as of 10:43, 21 February 2008
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Crystal structure of human microurokinase in complex with 2-amino-5-hydroxy-benzimidazole
Contents |
Overview
Using an NMR-based screen, a novel class of urokinase inhibitors were identified that contain a 2-aminobenzimidazole moiety. The inhibitory potency of this family of inhibitors is similar to that of inhibitors containing a guanidine or amidine group. However, unlike previously described guanidino- or amidino-based inhibitors which have pK(a) values greater than 9.0, urokinase inhibitors containing a 2-aminobenzimidazole have pK(a) values of 7.5. Thus, 2-aminobenzimidazoles may have improved pharmacokinetic properties which could increase the bioavailability of inhibitors which contain this moiety. A crystal structure of one of the lead inhibitors, 2-amino-5-hydroxybenzimidazole, complexed with urokinase reveals the electrostatic and hydrophobic interactions that stabilize complex formation and suggests nearby subsites that may be accessed to increase the potency of this new series of urokinase inhibitors.
Disease
Known disease associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[191840]
About this Structure
1FV9 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as U-plasminogen activator, with EC number 3.4.21.73 Full crystallographic information is available from OCA.
Reference
Identification of novel inhibitors of urokinase via NMR-based screening., Hajduk PJ, Boyd S, Nettesheim D, Nienaber V, Severin J, Smith R, Davidson D, Rockway T, Fesik SW, J Med Chem. 2000 Oct 19;43(21):3862-6. PMID:11052791
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