2ea2: Difference between revisions

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Revision as of 17:37, 20 March 2008

File:2ea2.jpg

, resolution 2.50Å

Sites:

, and

Ligands:

and

Activity:

Methionyl aminopeptidase, with EC number 3.4.11.18

Coordinates:

save as pdb, mmCIF, xml

h-MetAP2 complexed with A773812

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

2EA2 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 Thu Mar 20 16:37:22 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:2ea2.jpg|left|200px]]<br /><applet load="2ea2" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2ea2.jpg|left|200px]]
-caption="2ea2, resolution 2.50&Aring;" />
-'''h-MetAP2 complexed with A773812'''<br />
+ {{Structure
+|PDB= 2ea2 |SIZE=350|CAPTION= <scene name='initialview01'>2ea2</scene>, resolution 2.50&Aring;
+|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:F77+Binding+Site+For+Residue+A+482'>AC3</scene>
+|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> and <scene name='pdbligand=F77:'>F77</scene>
+|ACTIVITY= [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]
+|GENE=
+}}
+'''h-MetAP2 complexed with A773812'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-EA2 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=MN:'>MN</scene> and <scene name='pdbligand=F77:'>F77</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Sites: <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:F77+Binding+Site+For+Residue+A+482'>AC3</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EA2 OCA].
+EA2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EA2 OCA].
 ==Reference==
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17350258 17350258]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/17350258 17350258]
 [[Category: Homo sapiens]]
 [[Category: Methionyl aminopeptidase]]
@@ Line 20: / Line 29: @@
 [[Category: protein-ligand complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:07:51 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:37:22 2008''