3p2x: Difference between revisions

Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(6 intermediate revisions by the same user not shown)
Line 1: Line 1:
{{STRUCTURE_3p2x|  PDB=3p2x  |  SCENE=  }}
===Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity===
{{ABSTRACT_PUBMED_15794638}}


==Disease==
==Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity==
[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[http://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:[http://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:[http://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:[http://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>  
<StructureSection load='3p2x' size='340' side='right'caption='[[3p2x]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3p2x]] 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=3P2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P2X 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&#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=DAL:D-ALANINE'>DAL</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=3p2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2x OCA], [https://pdbe.org/3p2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p2x RCSB], [https://www.ebi.ac.uk/pdbsum/3p2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2x 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SINCE insulin was first shown by Scott to crystallize in the presence of zinc ions in 1934, a variety of Zn-containing insulin crystals have been grown. The structures of insulin in the related rhombohedral crystals of 2Zn-insulin and 4Zn-insulin have been solved and reveal that the molecule is a hexamer, organized as three dimers, each containing a 2-fold symmetry axis and held together by Zn ions. In 2Zn-insulin the hexamer is nearly symmetrical with the two axial Zn ions and the two molecules of the dimer related closely by a local 2-fold axis. But in 4Zn-insulin the two molecules in the dimer differ remarkably, creating an asymmetric 4Zn-hexamer in which one trimer is essentially equivalent to that in 2Zn-insulin and the other is different by virtue of an additional stretch of N-terminal helix between residues B1 and B8 (refs 6, 7). We report here the structure of a new symmetrical hexamer, in which all six molecules have the B1-B8 helix seen in 4Zn-insulin. Phenol molecules, found bonding specifically to each molecule, evidently stabilize this new helical conformation.


==Function==
Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer.,Derewenda U, Derewenda Z, Dodson EJ, Dodson GG, Reynolds CD, Smith GD, Sparks C, Swenson D Nature. 1989 Apr 13;338(6216):594-6. PMID:002648161<ref>PMID:002648161</ref>
[[http://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.  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[3p2x]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2X OCA].
</div>
<div class="pdbe-citations 3p2x" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Molecular Playground/Insulin|Molecular Playground/Insulin]]
*[[Insulin 3D Structures|Insulin 3D Structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:015794638</ref><ref group="xtra">PMID:014596591</ref><ref group="xtra">PMID:015610006</ref><ref group="xtra">PMID:002905485</ref><ref group="xtra">PMID:002648161</ref><references group="xtra"/><references/>
__TOC__
[[Category: Dodson, G G.]]
</StructureSection>
[[Category: Hu, S Q.]]
[[Category: Homo sapiens]]
[[Category: Hua, Q X.]]
[[Category: Large Structures]]
[[Category: Huang, K.]]
[[Category: Dodson GG]]
[[Category: Jia, W H.]]
[[Category: Hu SQ]]
[[Category: Katsoyannis, P G.]]
[[Category: Hua QX]]
[[Category: Phillip, N F.]]
[[Category: Huang K]]
[[Category: Wan, Z L.]]
[[Category: Jia WH]]
[[Category: Weiss, M A.]]
[[Category: Katsoyannis PG]]
[[Category: Whittingham, J.]]
[[Category: Phillip NF]]
[[Category: Global health]]
[[Category: Wan ZL]]
[[Category: Hormone]]
[[Category: Weiss MA]]
[[Category: Insulin fibrillation]]
[[Category: Whittingham J]]
[[Category: Long-acting insulin analog]]
[[Category: Receptor binding protein engineering]]
[[Category: Zinc-binding site]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/w/3p2x"