2h04: Difference between revisions

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[[Image:2h04.gif|left|200px]]
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{{STRUCTURE_2h04|  PDB=2h04  |  SCENE=  }}
'''Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors'''


==Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors==
<StructureSection load='2h04' size='340' side='right'caption='[[2h04]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2h04]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H04 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4UN:{4-[2,2-BIS(5-METHYL-1,2,4-OXADIAZOL-3-YL)-3-PHENYLPROPYL]PHENYL}SULFAMIC+ACID'>4UN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2h04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h04 OCA], [https://pdbe.org/2h04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h04 RCSB], [https://www.ebi.ac.uk/pdbsum/2h04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h04 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PTPRB_HUMAN PTPRB_HUMAN] Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin (By similarity).<ref>PMID:19116766</ref> <ref>PMID:19136612</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h0/2h04_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2h04 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The sulfamic acid phosphotyrosine mimetic was coupled with a previously known malonate template to obtain highly selective and potent inhibitors of HPTPbeta. Potentially hydrolyzable malonate ester functionalities were replaced with 1,2,4-oxadiazoles without a significant effect on HPTPbeta potency.


==Overview==
Design and synthesis of potent, non-peptidic inhibitors of HPTPbeta.,Amarasinghe KK, Evdokimov AG, Xu K, Clark CM, Maier MB, Srivastava A, Colson AO, Gerwe GS, Stake GE, Howard BW, Pokross ME, Gray JL, Peters KG Bioorg Med Chem Lett. 2006 Aug 15;16(16):4252-6. Epub 2006 Jun 12. PMID:16759857<ref>PMID:16759857</ref>
The sulfamic acid phosphotyrosine mimetic was coupled with a previously known malonate template to obtain highly selective and potent inhibitors of HPTPbeta. Potentially hydrolyzable malonate ester functionalities were replaced with 1,2,4-oxadiazoles without a significant effect on HPTPbeta potency.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2H04 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=2H04 OCA].
</div>
<div class="pdbe-citations 2h04" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Design and synthesis of potent, non-peptidic inhibitors of HPTPbeta., Amarasinghe KK, Evidokimov AG, Xu K, Clark CM, Maier MB, Srivastava A, Colson AO, Gerwe GS, Stake GE, Howard BW, Pokross ME, Gray JL, Peters KG, Bioorg Med Chem Lett. 2006 Aug 15;16(16):4252-6. Epub 2006 Jun 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16759857 16759857]
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Amarasinghe KD]]
[[Category: Amarasinghe, K D.]]
[[Category: Clark CM]]
[[Category: Clark, C M.]]
[[Category: Evdokimov AG]]
[[Category: Evdokimov, A G.]]
[[Category: Gray JL]]
[[Category: Gray, J L.]]
[[Category: Maier MB]]
[[Category: Maier, M B.]]
[[Category: Mekel M]]
[[Category: Mekel, M.]]
[[Category: Nichols R]]
[[Category: Nichols, R.]]
[[Category: Peters KG]]
[[Category: Peters, K G.]]
[[Category: Pokross ME]]
[[Category: Pokross, M E.]]
[[Category: Walter RL]]
[[Category: Walter, R L.]]
[[Category: Drug design]]
[[Category: Inhibitor]]
[[Category: Phosphatase]]
[[Category: Protein tyrosine phosphatase]]
[[Category: Sulfamic acid]]
[[Category: Wpd-loop]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:42:41 2008''

Latest revision as of 12:49, 30 August 2023

Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitorsStructural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors

Structural highlights

2h04 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PTPRB_HUMAN Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin (By similarity).[1] [2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The sulfamic acid phosphotyrosine mimetic was coupled with a previously known malonate template to obtain highly selective and potent inhibitors of HPTPbeta. Potentially hydrolyzable malonate ester functionalities were replaced with 1,2,4-oxadiazoles without a significant effect on HPTPbeta potency.

Design and synthesis of potent, non-peptidic inhibitors of HPTPbeta.,Amarasinghe KK, Evdokimov AG, Xu K, Clark CM, Maier MB, Srivastava A, Colson AO, Gerwe GS, Stake GE, Howard BW, Pokross ME, Gray JL, Peters KG Bioorg Med Chem Lett. 2006 Aug 15;16(16):4252-6. Epub 2006 Jun 12. PMID:16759857[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Yacyshyn OK, Lai PF, Forse K, Teichert-Kuliszewska K, Jurasz P, Stewart DJ. Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells. Angiogenesis. 2009;12(1):25-33. doi: 10.1007/s10456-008-9126-0. Epub 2009 Jan 1. PMID:19116766 doi:10.1007/s10456-008-9126-0
  2. ↑ Mellberg S, Dimberg A, Bahram F, Hayashi M, Rennel E, Ameur A, Westholm JO, Larsson E, Lindahl P, Cross MJ, Claesson-Welsh L. Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis. FASEB J. 2009 May;23(5):1490-502. doi: 10.1096/fj.08-123810. Epub 2009 Jan 9. PMID:19136612 doi:http://dx.doi.org/10.1096/fj.08-123810
  3. ↑ Amarasinghe KK, Evdokimov AG, Xu K, Clark CM, Maier MB, Srivastava A, Colson AO, Gerwe GS, Stake GE, Howard BW, Pokross ME, Gray JL, Peters KG. Design and synthesis of potent, non-peptidic inhibitors of HPTPbeta. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4252-6. Epub 2006 Jun 12. PMID:16759857 doi:10.1016/j.bmcl.2006.05.074

2h04, resolution 2.30Å

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