2hh4

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2hh4.gif|left|200px]]<br /><applet load="2hh4" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:2hh4.gif|left|200px]]
-
caption="2hh4" />
+
 
-
'''NMR structure of human insulin mutant GLY-B8-D-SER, HIS-B10-ASP PRO-B28-LYS, LYS-B29-PRO, 20 structures'''<br />
+
{{Structure
 +
|PDB= 2hh4 |SIZE=350|CAPTION= <scene name='initialview01'>2hh4</scene>
 +
|SITE=
 +
|LIGAND=
 +
|ACTIVITY=
 +
|GENE= INS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
 +
}}
 +
 
 +
'''NMR structure of human insulin mutant GLY-B8-D-SER, HIS-B10-ASP PRO-B28-LYS, LYS-B29-PRO, 20 structures'''
 +
 
==Overview==
==Overview==
Line 10: Line 19:
==About this Structure==
==About this Structure==
-
2HH4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=2HH4 OCA].
+
2HH4 is a [[Protein complex]] structure of sequences 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=2HH4 OCA].
==Reference==
==Reference==
-
Toward the active conformation of insulin: stereospecific modulation of a structural switch in the B chain., Hua QX, Nakagawa S, Hu SQ, Jia W, Wang S, Weiss MA, J Biol Chem. 2006 Aug 25;281(34):24900-9. Epub 2006 Jun 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16762918 16762918]
+
Toward the active conformation of insulin: stereospecific modulation of a structural switch in the B chain., Hua QX, Nakagawa S, Hu SQ, Jia W, Wang S, Weiss MA, J Biol Chem. 2006 Aug 25;281(34):24900-9. Epub 2006 Jun 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16762918 16762918]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
Line 25: Line 34:
[[Category: mutant]]
[[Category: mutant]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:41:49 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:17:02 2008''

Revision as of 15:17, 20 March 2008

Image:2hh4.gif


PDB ID 2hh4

Drag the structure with the mouse to rotate
Gene: INS (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



NMR structure of human insulin mutant GLY-B8-D-SER, HIS-B10-ASP PRO-B28-LYS, LYS-B29-PRO, 20 structures


Contents

Overview

How insulin binds to the insulin receptor has long been a subject of speculation. Although the structure of the free hormone has been extensively characterized, a variety of evidence suggests that a conformational change occurs upon receptor binding. Here, we employ chiral mutagenesis, comparison of corresponding d and l amino acid substitutions, to investigate a possible switch in the B-chain. To investigate the interrelation of structure, function, and stability, isomeric analogs have been synthesized in which an invariant glycine in a beta-turn (Gly(B8)) is replaced by d- or l-Ser. The d substitution enhances stability (DeltaDeltaG(u) 0.9 kcal/mol) but impairs receptor binding by 100-fold; by contrast, the l substitution markedly impairs stability (DeltaDeltaG(u) -3.0 kcal/mol) with only 2-fold reduction in receptor binding. Although the isomeric structures each retain a native-like overall fold, the l-Ser(B8) analog exhibits fewer helix-related and long range nuclear Overhauser effects than does the d-Ser(B8) analog or native monomer. Evidence for enhanced conformational fluctuations in the unstable analog is provided by its attenuated CD spectrum. The inverse relationship between stereospecific stabilization and receptor binding strongly suggests that the B7-B10 beta-turn changes conformation on receptor binding.

Disease

Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]

About this Structure

2HH4 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Toward the active conformation of insulin: stereospecific modulation of a structural switch in the B chain., Hua QX, Nakagawa S, Hu SQ, Jia W, Wang S, Weiss MA, J Biol Chem. 2006 Aug 25;281(34):24900-9. Epub 2006 Jun 8. PMID:16762918

Page seeded by OCA on Thu Mar 20 17:17:02 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hh4"
Personal tools