3kr3: Difference between revisions

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-[[Image:3kr3.png|left|200px]]
-{{STRUCTURE_3kr3|  PDB=3kr3  |  SCENE=  }}
+==Crystal structure of IGF-II antibody complex==
+<StructureSection load='3kr3' size='340' side='right'caption='[[3kr3]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3kr3]] is a 3 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=3KR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KR3 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=3kr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kr3 OCA], [https://pdbe.org/3kr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kr3 RCSB], [https://www.ebi.ac.uk/pdbsum/3kr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kr3 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN] Epigenetic changes of DNA hypomethylation in IGF2 are a cause of Silver-Russell syndrome (SRS) [MIM:[https://omim.org/entry/180860 180860]. A clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age.<ref>PMID:19066168</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN] The insulin-like growth factors possess growth-promoting activity. In vitro, they are potent mitogens for cultured cells. IGF-II is influenced by placental lactogen and may play a role in fetal development.<ref>PMID:16912056</ref>   Preptin undergoes glucose-mediated co-secretion with insulin, and acts as physiological amplifier of glucose-mediated insulin secretion. Exhibits osteogenic properties by increasing osteoblast mitogenic activity through phosphoactivation of MAPK1 and MAPK3.<ref>PMID:16912056</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/kr/3kr3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3kr3 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Elevated expression of insulin-like growth factor-II (IGF-II) is frequently observed in a variety of human malignancies, including breast, colon, and liver cancer. As IGF-II can deliver a mitogenic signal through both IGF-IR and an alternately spliced form of the insulin receptor (IR-A), neutralizing the biological activity of this growth factor directly is a potential alternative option to IGF-IR-directed agents. Using a Fab-displaying phage library and a biotinylated precursor form of IGF-II (1-104 amino acids) as a target, we isolated Fabs specific for the E-domain COOH-terminal extension form of IGF-II and for mature IGF-II. One of these Fabs that bound to both forms of IGF-II was reformatted into a full-length IgG, expressed, purified, and subjected to further analysis. This antibody (DX-2647) displayed a very high affinity for IGF-II/IGF-IIE (K(D) value of 49 and 10 pmol/L, respectively) compared with IGF-I (approximately 10 nmol/L) and blocked binding of IGF-II to IGF-IR, IR-A, a panel of insulin-like growth factor-binding proteins, and the mannose-6-phosphate receptor. A crystal complex of the parental Fab of DX-2647 bound to IGF-II was resolved to 2.2 A. DX-2647 inhibited IGF-II and, to a lesser extent, IGF-I-induced receptor tyrosine phosphorylation, cellular proliferation, and both anchorage-dependent and anchorage-independent colony formation in various cell lines. In addition, DX-2647 slowed tumor progression in the Hep3B xenograft model, causing decreased tumoral CD31 staining as well as reduced IGF-IIE and IGF-IR phosphorylation levels. Therefore, DX-2647 offers an alternative approach to targeting IGF-IR, blocking IGF-II signaling through both IGF-IR and IR-A.
-===Crystal structure of IGF-II antibody complex===
+A human monoclonal antibody against insulin-like growth factor-II blocks the growth of human hepatocellular carcinoma cell lines in vitro and in vivo.,Dransfield DT, Cohen EH, Chang Q, Sparrow LG, Bentley JD, Dolezal O, Xiao X, Peat TS, Newman J, Pilling PA, Phan T, Priebe I, Brierley GV, Kastrapeli N, Kopacz K, Martik D, Wassaf D, Rank D, Conley G, Huang Y, Adams TE, Cosgrove L Mol Cancer Ther. 2010 Jun;9(6):1809-19. Epub 2010 Jun 1. PMID:20515953<ref>PMID:20515953</ref>
-{{ABSTRACT_PUBMED_20515953}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3kr3" style="background-color:#fffaf0;"></div>
-[[3kr3]] is a 3 chain structure with 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=3KR3 OCA].
 ==See Also==
-*[[Antibody|Antibody]]
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[Insulin-like growth factor|Insulin-like growth factor]]
-==Reference==
+*[[3D structures of human antibody|3D structures of human antibody]]
-<ref group="xtra">PMID:020515953</ref><references group="xtra"/>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Adams, T E.]]
+[[Category: Large Structures]]
-[[Category: Newman, J.]]
+[[Category: Adams TE]]
-[[Category: Peat, T S.]]
+[[Category: Newman J]]
-[[Category: Antibody-target complex]]
+[[Category: Peat TS]]
-[[Category: Carbohydrate metabolism]]
-[[Category: Glucose metabolism]]
-[[Category: Glycoprotein]]
-[[Category: Growth factor]]
-[[Category: Hormone]]
-[[Category: Immune system]]
-[[Category: Mitogen]]
-[[Category: Osteogenesis]]
-[[Category: Secreted]]