2ea4: Difference between revisions

Revision as of 02:13, 4 May 2008

h-MetAP2 complexed with A797859

OverviewOverview

A series of aryl sulfonamides of 5,6-disubstituted anthranilic acids were identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2). Small alkyl groups and 3-furyl were tolerated at the 5-position of anthranilic acid, while -OCH(3), CH(3), and Cl were found optimal for the 6-position. Placement of 2-aminoethoxy group at the 6-position enabled interaction with the second Mn(2+) but did not result in enhancement in potency. Introduction of a tertiary amino moiety at the ortho-position of the sulfonyl phenyl ring gave reduced protein binding and improved cellular activity, but led to lower oral bioavailability.

About this StructureAbout this Structure

2EA4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids., Wang GT, Mantei RA, Kawai M, Tedrow JS, Barnes DM, Wang J, Zhang Q, Lou P, Garcia LA, Bouska J, Yates M, Park C, Judge RA, Lesniewski R, Sheppard GS, Bell RL, Bioorg Med Chem Lett. 2007 May 15;17(10):2817-22. Epub 2007 Feb 25. PMID:17350258 Page seeded by OCA on Sun May 4 02:13:49 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:2ea4.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2ea4 |SIZE=350|CAPTION= <scene name='initialview01'>2ea4</scene>, resolution 2.35&Aring;
+The line below this paragraph, containing "STRUCTURE_2ea4", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Mn+Binding+Site+For+Residue+A+480'>AC1</scene>, <scene name='pdbsite=AC2:Mn+Binding+Site+For+Residue+A+481'>AC2</scene> and <scene name='pdbsite=AC3:F79+Binding+Site+For+Residue+A+482'>AC3</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=F79:2-(2-AMINOETHOXY)-3-ETHYL-6-{[(4-FLUOROPHENYL)SULFONYL]AMINO}BENZOIC+ACID'>F79</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.18 3.4.11.18] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2ea4|  PDB=2ea4  |  SCENE=  }}
-|RELATEDENTRY=[[1yw7|1YW7]], [[1yw8|1YW8]], [[1yw9|1YW9]], [[2ga2|2GA2]], [[2ea2|2EA2]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ea4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ea4 OCA], [http://www.ebi.ac.uk/pdbsum/2ea4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ea4 RCSB]</span>
-}}
 '''h-MetAP2 complexed with A797859'''
@@ Line 27: / Line 24: @@
 [[Category: Single protein]]
 [[Category: Park, C H.]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: protein-ligand complex]]
+[[Category: Protein-ligand complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 02:13:49 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:46:04 2008''