View source for 1ben


==INSULIN COMPLEXED WITH 4-HYDROXYBENZAMIDE==
<StructureSection load='1ben' size='340' side='right'caption='[[1ben]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ben]] is a 4 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=1BEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BEN 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]] 1.4&#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=HBD:4-HYDROXYBENZAMIDE'>HBD</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=1ben FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ben OCA], [https://pdbe.org/1ben PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ben RCSB], [https://www.ebi.ac.uk/pdbsum/1ben PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ben 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/be/1ben_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=1ben ConSurf].
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== Publication Abstract from PubMed ==
The structure of a symmetric T3R3f insulin hexamer, complexed with 4-hydroxybenzamide, has been determined using X-ray crystallographic techniques. Data were measured from six crystals grown in microgravity to a resolution of 1.4 A and the structure has been refined including the contributions from hydrogen atoms. The crystals are isomorphous with T3R3f complexes of phenolic derivatives as well as with uncomplexed forms. Unlike the structures of complexes with phenol, m-cresol, resorcinol, 4'-hydroxyacetanilide, and methylparaben, which bind one phenolic derivative molecule per R- or Rf-state monomer, two molecules of 4-hydroxybenzamide are bound by each Rf-state monomer. The presence of the second guest molecule results in an extensive hydrogen bonding network, mediated by water molecules, between the T- and Rf-state trimers and adds stability to the formation of the hexamer. The only access to these second sites is through three symmetry-related, narrow channels that originate on the surface of the T-state trimer. Although the conformation of the backbone atoms of the monomers is nearly identical to that of other T3R3f hexamers, significant changes are observed in the conformations of side chains in the vicinity of the second binding site. The side chain of the T-state A11 Cys residue, which forms a disulfide bond to A6 Cys in the same monomer, is observed in two discrete conformations; two discrete conformations are also present for the entire A8 Thr residue in the Rf-state monomer. A procedure is also described for an alternate method of interframe scaling and merging intensity data from an image plate detector.

A novel complex of a phenolic derivative with insulin: structural features related to the T--&gt;R transition.,Smith GD, Ciszak E, Pangborn W Protein Sci. 1996 Aug;5(8):1502-11. PMID:8844841<ref>PMID:8844841</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1ben" style="background-color:#fffaf0;"></div>

==See Also==
*[[Insulin 3D Structures|Insulin 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ciszak E]]
[[Category: Pangborn W]]
[[Category: Smith GD]]