4ge5: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ge5]] is a 2 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=4GE5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GE5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ge5]] is a 2 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=4GE5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GE5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A89:N-(4-BROMO-3-METHYLBENZOYL)-4-[DIFLUORO(PHOSPHONO)METHYL]-L-PHENYLALANYL-N~5~-(3-IODOBENZOYL)-L-ORNITHINAMIDE'>A89</scene></td></tr>
</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A89:N-(4-BROMO-3-METHYLBENZOYL)-4-[DIFLUORO(PHOSPHONO)METHYL]-L-PHENYLALANYL-N~5~-(3-IODOBENZOYL)-L-ORNITHINAMIDE'>A89</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=4ge5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ge5 OCA], [https://pdbe.org/4ge5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ge5 RCSB], [https://www.ebi.ac.uk/pdbsum/4ge5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ge5 ProSAT]</span></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=4ge5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ge5 OCA], [https://pdbe.org/4ge5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ge5 RCSB], [https://www.ebi.ac.uk/pdbsum/4ge5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ge5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/PTN9_HUMAN PTN9_HUMAN] Protein-tyrosine phosphatase that could participate in the transfer of hydrophobic ligands or in functions of the Golgi apparatus.
[https://www.uniprot.org/uniprot/PTN9_HUMAN PTN9_HUMAN] Protein-tyrosine phosphatase that could participate in the transfer of hydrophobic ligands or in functions of the Golgi apparatus.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein tyrosine phosphatases (PTPs) constitute a large family of signaling enzymes that control the cellular levels of protein tyrosine phosphorylation. A detailed understanding of PTP functions in normal physiology and in pathogenic conditions has been hampered by the absence of PTP-specific, cell-permeable small-molecule agents. We present a stepwise focused library approach that transforms a weak and general non-hydrolyzable pTyr mimetic (F(2)Pmp, phosphonodifluoromethyl phenylalanine) into a highly potent and selective inhibitor of PTP-MEG2, an antagonist of hepatic insulin signaling. The crystal structures of the PTP-MEG2-inhibitor complexes provide direct evidence that potent and selective PTP inhibitors can be obtained by introducing molecular diversity into the F(2)Pmp scaffold to engage both the active site and unique nearby peripheral binding pockets. Importantly, the PTP-MEG2 inhibitor possesses highly efficacious cellular activity and is capable of augmenting insulin signaling and improving insulin sensitivity and glucose homeostasis in diet-induced obese mice. The results indicate that F(2)Pmp can be converted into highly potent and selective PTP inhibitory agents with excellent in vivo efficacy. Given the general nature of the approach, this strategy should be applicable to other members of the PTP superfamily.
A Highly Selective and Potent PTP-MEG2 Inhibitor with Therapeutic Potential for Type 2 Diabetes.,Zhang S, Liu S, Tao R, Wei D, Chen L, Shen W, Yu ZH, Wang L, Jones DR, Dong XC, Zhang ZY J Am Chem Soc. 2012 Oct 31;134(43):18116-24. doi: 10.1021/ja308212y. Epub 2012, Oct 17. PMID:23075115<ref>PMID:23075115</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ge5" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Latest revision as of 15:44, 14 March 2024

Crystal structure of human protein tyrosine phosphatase PTPN9 (MEG2) complex with compound 5

4ge5, resolution 2.00Å

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