1fv9: Difference between revisions

Revision as of 16:48, 2 May 2008

Crystal structure of human microurokinase in complex with 2-amino-5-hydroxy-benzimidazole

OverviewOverview

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.

About this StructureAbout this Structure

1FV9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Fri May 2 16:48:08 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1fv9.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1fv9 |SIZE=350|CAPTION= <scene name='initialview01'>1fv9</scene>, resolution 3.00&Aring;
+The line below this paragraph, containing "STRUCTURE_1fv9", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=172:2-AMINO-5-HYDROXY-BENZIMIDAZOLE'>172</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1fv9|  PDB=1fv9  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fv9 OCA], [http://www.ebi.ac.uk/pdbsum/1fv9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1fv9 RCSB]</span>
-}}
 '''Crystal structure of human microurokinase in complex with 2-amino-5-hydroxy-benzimidazole'''
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 [[Category: U-plasminogen activator]]
 [[Category: Nienaber, V.]]
-[[Category: plasminogen activation]]
+[[Category: Plasminogen activation]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 16:48:08 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:30:57 2008''