7ppm: Difference between revisions

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-'''Unreleased structure'''
-The entry 7ppm is ON HOLD
+==SHP2 catalytic domain in complex with IRS1 (889-901) phosphopeptide (pSer-892, pTyr-896)==
+<StructureSection load='7ppm' size='340' side='right'caption='[[7ppm]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7ppm]] 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=7PPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PPM 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]] 1.48&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=7ppm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ppm OCA], [https://pdbe.org/7ppm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ppm RCSB], [https://www.ebi.ac.uk/pdbsum/7ppm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ppm ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN] Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:[https://omim.org/entry/151100 151100]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref>   Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[https://omim.org/entry/163950 163950]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref>   Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[https://omim.org/entry/607785 607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.<ref>PMID:12717436</ref>   Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:[https://omim.org/entry/156250 156250]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions.<ref>PMID:20577567</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN] Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity.<ref>PMID:10655584</ref> <ref>PMID:18829466</ref> <ref>PMID:18559669</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Serine/threonine phosphorylation of insulin receptor substrate (IRS) proteins is well known to modulate insulin signaling. However, the molecular details of this process have mostly been elusive. While exploring the role of phosphoserines, we have detected a direct link between Tyr-flanking Ser/Thr phosphorylation sites and regulation of specific phosphotyrosine phosphatases. Here we present a concise structural study on how the activity of SHP2 phosphatase is controlled by an asymmetric, dual phosphorylation of its substrates. The structure of SHP2 has been determined with three different substrate peptides, unveiling the versatile and highly dynamic nature of substrate recruitment. What is more, the relatively stable pre-catalytic state of SHP2 could potentially be useful for inhibitor design. Our findings not only show an unusual dependence of SHP2 catalytic activity on Ser/Thr phosphorylation sites in IRS1 and CD28, but also suggest a negative regulatory mechanism that may also apply to other tyrosine kinase pathways as well.
-Authors: Sok, P., Zeke, A., Remenyi, A.
+Structural insights into the pSer/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling.,Zeke A, Takacs T, Sok P, Nemeth K, Kirsch K, Egri P, Poti AL, Bento I, Tusnady GE, Remenyi A Nat Commun. 2022 Sep 16;13(1):5439. doi: 10.1038/s41467-022-32918-5. PMID:36114179<ref>PMID:36114179</ref>
-Description: SHP2 catalytic domain in complex with IRS1 (889-901) phosphopeptide (pSer-892, pTyr-896)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Remenyi, A]]
+<div class="pdbe-citations 7ppm" style="background-color:#fffaf0;"></div>
-[[Category: Sok, P]]
-[[Category: Zeke, A]]
+==See Also==
+*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Remenyi A]]
+[[Category: Sok P]]
+[[Category: Zeke A]]