2hiu: Difference between revisions

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~~[[Image:2hiu.gif|left|200px]]<br />~~

~~<applet load="2hiu" size="450" color="white" frame="true" align="right" spinBox="true"~~

~~caption="2hiu" />~~

~~'''NMR STRUCTURE OF HUMAN INSULIN IN 20% ACETIC ACID, ZINC-FREE, 10 STRUCTURES'''<br />~~

==~~Overview~~==

==NMR STRUCTURE OF HUMAN INSULIN IN 20% ACETIC ACID, ZINC-FREE, 10 STRUCTURES==

We have determined the structure of a metastable disulphide isomer of, human insulin. Although not observed for proinsulin folding or, insulin-chain recombination, the isomer retains ordered secondary, structure and a compact hydrophobic core. Comparison with native insulin, reveals a global rearrangement in the orientation of A- and B-chains. One, face of the protein's surface is nevertheless in common between native and, non-native structures. This face contains receptor-binding determinants, rationalizing the partial biological activity of the isomer. Structures of, native and non-native disulphide isomers also define alternative, three-dimensional templates. Threading of insulin-like sequences provide, an experimental realization of the inverse protein-folding problem.

== Structural highlights ==

<table><tr><td colspan='2'>[[2hiu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1hiu 1hiu]. The February 2001 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Insulin'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2001_2 10.2210/rcsb_pdb/mom_2001_2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HIU FirstGlance]. <br>

</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=2hiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hiu OCA], [https://pdbe.org/2hiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hiu RCSB], [https://www.ebi.ac.uk/pdbsum/2hiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hiu 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>

<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hi/2hiu_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=2hiu ConSurf].

== Publication Abstract from PubMed ==

We have determined the structure of a metastable disulphide isomer of human insulin. Although not observed for proinsulin folding or insulin-chain recombination, the isomer retains ordered secondary structure and a compact hydrophobic core. Comparison with native insulin reveals a global rearrangement in the orientation of A- and B-chains. One face of the protein's surface is nevertheless in common between native and non-native structures. This face contains receptor-binding determinants, rationalizing the partial biological activity of the isomer. Structures of native and non-native disulphide isomers also define alternative three-dimensional templates. Threading of insulin-like sequences provide an experimental realization of the inverse protein-folding problem.

~~==Disease==~~

Structure of a protein in a kinetic trap.,Hua QX, Gozani SN, Chance RE, Hoffmann JA, Frank BH, Weiss MA Nat Struct Biol. 1995 Feb;2(2):129-38. PMID:7749917<ref>PMID:7749917</ref>

~~Known diseases associated with this structure: Diabetes mellitus~~, ~~rare form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]]~~, ~~Hyperproinsulinemia~~, ~~familial OMIM:[[http~~:~~//www~~.~~ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], MODY, one form OMIM~~:~~[[http~~:/~~/www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]]~~

~~==About this Structure==~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

~~2HIU is~~ a ~~[http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure~~ of ~~sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]~~. ~~This structure superseeds the now removed PDB entry 1HIU~~. ~~The following page contains interesting information on the relation~~ of ~~2HIU with [[http://pdb~~.~~rcsb.org~~/~~pdb/static.do?p~~=~~education_discussion/molecule_of_the_month/pdb14_1.html Insulin]]. Full crystallographic information is available from [http~~:/~~/ispc.weizmann.ac.il/oca-bin/ocashort?id=2HIU OCA].~~

</div>

==~~Reference~~==

==See Also==

~~Structure of a protein in a kinetic trap., Hua QX, Gozani SN, Chance RE, Hoffmann JA, Frank BH, Weiss MA, Nat Struct Biol. 1995 Feb;2(2):129-38. PMID:~~[~~http:~~//~~ispc.weizmann.ac.il//pmbin/getpm?pmid=7749917 7749917]~~

*[[Insulin 3D Structures|Insulin 3D Structures]]

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Insulin]]

[[Category: ~~Protein complex~~]]

[[Category: Large Structures]]

[[Category: Chance, R.E.]]

[[Category: RCSB PDB Molecule of the Month]]

[[Category: Frank, B.H.]]

[[Category: Chance, R E]]

[[Category: Gozani, S.N.]]

[[Category: Frank, B H]]

[[Category: Hoffmann, J.A.]]

[[Category: Gozani, S N]]

[[Category: Hua, Q.X.]]

[[Category: Hoffmann, J A]]

[[Category: Weiss, M.A.]]

[[Category: Hua, Q X]]

[[Category: ~~glucose~~ metabolism]]

[[Category: Weiss, M A]]

[[Category: ~~hormone~~]]

[[Category: Glucose metabolism]]

~~[[Category: insulin]]~~

[[Category: Hormone]]

~~''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:33:07 2007''~~

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@@ Line 1: / Line 1: @@
-[[Image:2hiu.gif|left|200px]]<br />
-<applet load="2hiu" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2hiu" />
-'''NMR STRUCTURE OF HUMAN INSULIN IN 20% ACETIC ACID, ZINC-FREE, 10 STRUCTURES'''<br />
-==Overview==
+==NMR STRUCTURE OF HUMAN INSULIN IN 20% ACETIC ACID, ZINC-FREE, 10 STRUCTURES==
-We have determined the structure of a metastable disulphide isomer of, human insulin. Although not observed for proinsulin folding or, insulin-chain recombination, the isomer retains ordered secondary, structure and a compact hydrophobic core. Comparison with native insulin, reveals a global rearrangement in the orientation of A- and B-chains. One, face of the protein's surface is nevertheless in common between native and, non-native structures. This face contains receptor-binding determinants, rationalizing the partial biological activity of the isomer. Structures of, native and non-native disulphide isomers also define alternative, three-dimensional templates. Threading of insulin-like sequences provide, an experimental realization of the inverse protein-folding problem.
+<StructureSection load='2hiu' size='340' side='right'caption='[[2hiu]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2hiu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1hiu 1hiu]. The February 2001 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Insulin''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2001_2 10.2210/rcsb_pdb/mom_2001_2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HIU FirstGlance]. <br>
+</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=2hiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hiu OCA], [https://pdbe.org/2hiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hiu RCSB], [https://www.ebi.ac.uk/pdbsum/2hiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hiu 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/hi/2hiu_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=2hiu ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+We have determined the structure of a metastable disulphide isomer of human insulin. Although not observed for proinsulin folding or insulin-chain recombination, the isomer retains ordered secondary structure and a compact hydrophobic core. Comparison with native insulin reveals a global rearrangement in the orientation of A- and B-chains. One face of the protein's surface is nevertheless in common between native and non-native structures. This face contains receptor-binding determinants, rationalizing the partial biological activity of the isomer. Structures of native and non-native disulphide isomers also define alternative three-dimensional templates. Threading of insulin-like sequences provide an experimental realization of the inverse protein-folding problem.
-==Disease==
+Structure of a protein in a kinetic trap.,Hua QX, Gozani SN, Chance RE, Hoffmann JA, Frank BH, Weiss MA Nat Struct Biol. 1995 Feb;2(2):129-38. PMID:7749917<ref>PMID:7749917</ref>
-Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], Hyperproinsulinemia, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], MODY, one form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-HIU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure superseeds the now removed PDB entry 1HIU. The following page contains interesting information on the relation of 2HIU with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb14_1.html Insulin]]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HIU OCA].
+</div>
+<div class="pdbe-citations 2hiu" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Structure of a protein in a kinetic trap., Hua QX, Gozani SN, Chance RE, Hoffmann JA, Frank BH, Weiss MA, Nat Struct Biol. 1995 Feb;2(2):129-38. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7749917 7749917]
+*[[Insulin 3D Structures|Insulin 3D Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
 [[Category: Insulin]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Chance, R.E.]]
+[[Category: RCSB PDB Molecule of the Month]]
-[[Category: Frank, B.H.]]
+[[Category: Chance, R E]]
-[[Category: Gozani, S.N.]]
+[[Category: Frank, B H]]
-[[Category: Hoffmann, J.A.]]
+[[Category: Gozani, S N]]
-[[Category: Hua, Q.X.]]
+[[Category: Hoffmann, J A]]
-[[Category: Weiss, M.A.]]
+[[Category: Hua, Q X]]
-[[Category: glucose metabolism]]
+[[Category: Weiss, M A]]
-[[Category: hormone]]
+[[Category: Glucose metabolism]]
-[[Category: insulin]]
+[[Category: Hormone]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:33:07 2007''