2qbr: Difference between revisions

Revision as of 14:41, 4 May 2008

Crystal structure of ptp1b-inhibitor complex

OverviewOverview

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. Starting with a high micromolar lead compound, structure-based optimization of novel PTP1B inhibitors by extension of the molecule from the enzyme active site into the second phosphotyrosine binding site is described. Medicinal chemistry, guided by X-ray complex structure and molecular modeling, has yielded low nanomolar PTP1B inhibitors in an efficient manner. Compounds from this chemical series were found to be actively transported into hepatocytes. This active uptake into target tissues could be one of the possible avenues to overcome the poor membrane permeability of PTP1B inhibitors.

About this StructureAbout this Structure

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

ReferenceReference

Structure-based optimization of protein tyrosine phosphatase 1B inhibitors: from the active site to the second phosphotyrosine binding site., Wilson DP, Wan ZK, Xu WX, Kirincich SJ, Follows BC, Joseph-McCarthy D, Foreman K, Moretto A, Wu J, Zhu M, Binnun E, Zhang YL, Tam M, Erbe DV, Tobin J, Xu X, Leung L, Shilling A, Tam SY, Mansour TS, Lee J, J Med Chem. 2007 Sep 20;50(19):4681-98. Epub 2007 Aug 17. PMID:17705360 Page seeded by OCA on Sun May 4 14:41:37 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:2qbr.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2qbr |SIZE=350|CAPTION= <scene name='initialview01'>2qbr</scene>, resolution 2.30&Aring;
+The line below this paragraph, containing "STRUCTURE_2qbr", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:910+Binding+Site+For+Residue+A+800'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=910:5-[3-(BENZYLAMINO)PHENYL]-4-BROMO-3-(CARBOXYMETHOXY)THIOPHENE-2-CARBOXYLIC+ACID'>910</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/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= PTPN1, PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2qbr|  PDB=2qbr  |  SCENE=  }}
-|RELATEDENTRY=[[2qbp|2QBP]], [[2qbq|2QBQ]], [[2qbs|2QBS]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qbr OCA], [http://www.ebi.ac.uk/pdbsum/2qbr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qbr RCSB]</span>
-}}
 '''Crystal structure of ptp1b-inhibitor complex'''
@@ Line 27: / Line 24: @@
 [[Category: Single protein]]
 [[Category: Xu, W.]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: protein-inhibitor complex]]
+[[Category: Protein-inhibitor complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:41:37 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:47:23 2008''