1qiy: Difference between revisions

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-[[Image:1qiy.gif|left|200px]]<br />
-<applet load="1qiy" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1qiy, resolution 2.3&Aring;" />
-'''HUMAN INSULIN HEXAMERS WITH CHAIN B HIS MUTATED TO TYR COMPLEXED WITH PHENOL'''<br />
-==Overview==
+==HUMAN INSULIN HEXAMERS WITH CHAIN B HIS MUTATED TO TYR COMPLEXED WITH PHENOL==
-The addition of phenols to hexameric insulin solutions produces a, particularly stable hexamer, resulting from a rearrangement in which, residues B1-B8 change from an extended conformation (T-state) to form an, alpha-helix (R-state). The R-state is, in part, stabilized by nonpolar, interactions between the phenolic molecule and residue B5 His at the, dimer-dimer interface. The B5 His --&gt; Tyr mutant human insulin was, constructed to see if the tyrosine side chain would mimic the effect of, phenol binding in the hexamer and induce the R-state. In partial support, of this hypothesis, the molecule crystallized as a half-helical hexamer, (T(3)R(3)) in conditions that conventionally promote the fully nonhelical, (T6) form. As expected, in the presence of phenol or resorcinol, the B5, Tyr ... [[http://ispc.weizmann.ac.il/pmbin/getpm?10508408 (full description)]]
+<StructureSection load='1qiy' size='340' side='right'caption='[[1qiy]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1qiy]] is a 12 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=1QIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QIY 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IPH:PHENOL'>IPH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1qiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qiy OCA], [https://pdbe.org/1qiy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qiy RCSB], [https://www.ebi.ac.uk/pdbsum/1qiy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qiy ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[https://omim.org/entry/176730 176730].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref>   Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[https://omim.org/entry/125852 125852]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref>   Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[https://omim.org/entry/606176 606176]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref>   Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[https://omim.org/entry/613370 613370]. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
+== 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/qi/1qiy_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=1qiy ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-QIY is a [[http://en.wikipedia.org/wiki/Protein_complex Protein complex]] structure of sequences from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with ZN, CL and IPH as [[http://en.wikipedia.org/wiki/ligands ligands]]. Structure known Active Sites: ZN1 and ZN2. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QIY OCA]].
+*[[Insulin 3D Structures|Insulin 3D Structures]]
+== References ==
-==Reference==
+<references/>
-Structural consequences of the B5 histidine --&gt; tyrosine mutation in human insulin characterized by X-ray crystallography and conformational analysis., Tang L, Whittingham JL, Verma CS, Caves LS, Dodson GG, Biochemistry. 1999 Sep 14;38(37):12041-51. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10508408 10508408]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Caves, L.S.D.]]
+[[Category: Caves LSD]]
-[[Category: Dodson, G.G.]]
+[[Category: Dodson GG]]
-[[Category: Tang, L.]]
+[[Category: Tang L]]
-[[Category: Verma, C.S.]]
+[[Category: Verma CS]]
-[[Category: Whittingham, J.L.]]
+[[Category: Whittingham JL]]
-[[Category: CL]]
-[[Category: IPH]]
-[[Category: ZN]]
-[[Category: diabetes]]
-[[Category: glucose metabolism]]
-[[Category: hormone]]
-[[Category: insulin mutant]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Oct 30 15:59:53 2007''