This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1kmf

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1kmf.gif|left|200px]]<br /><applet load="1kmf" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:1kmf.gif|left|200px]]
-
caption="1kmf" />
+
 
-
'''NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALLO-ILE, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES'''<br />
+
{{Structure
 +
|PDB= 1kmf |SIZE=350|CAPTION= <scene name='initialview01'>1kmf</scene>
 +
|SITE=
 +
|LIGAND=
 +
|ACTIVITY=
 +
|GENE=
 +
}}
 +
 
 +
'''NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALLO-ILE, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES'''
 +
 
==Overview==
==Overview==
Line 10: Line 19:
==About this Structure==
==About this Structure==
-
1KMF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KMF OCA].
+
1KMF is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KMF OCA].
==Reference==
==Reference==
-
Chiral mutagenesis of insulin's hidden receptor-binding surface: structure of an allo-isoleucine(A2) analogue., Xu B, Hua QX, Nakagawa SH, Jia W, Chu YC, Katsoyannis PG, Weiss MA, J Mol Biol. 2002 Feb 22;316(3):435-41. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11866509 11866509]
+
Chiral mutagenesis of insulin's hidden receptor-binding surface: structure of an allo-isoleucine(A2) analogue., Xu B, Hua QX, Nakagawa SH, Jia W, Chu YC, Katsoyannis PG, Weiss MA, J Mol Biol. 2002 Feb 22;316(3):435-41. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11866509 11866509]
[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Chu, Y C.]]
[[Category: Chu, Y C.]]
Line 26: Line 35:
[[Category: mutant]]
[[Category: mutant]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:35:41 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:19:22 2008''

Revision as of 10:19, 20 March 2008

Image:1kmf.gif


PDB ID 1kmf

Drag the structure with the mouse to rotate
Coordinates: save as pdb, mmCIF, xml



NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALLO-ILE, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES


Contents

Overview

The hydrophobic core of vertebrate insulins contains an invariant isoleucine residue at position A2. Lack of variation may reflect this side-chain's dual contribution to structure and function: Ile(A2) is proposed both to stabilize the A1-A8 alpha-helix and to contribute to a "hidden" functional surface exposed on receptor binding. Substitution of Ile(A2) by alanine results in segmental unfolding of the A1-A8 alpha-helix, lower thermodynamic stability and impaired receptor binding. Such a spectrum of perturbations, although of biophysical interest, confounds interpretation of structure-activity relationships. To investigate the specific contribution of Ile(A2) to insulin's functional surface, we have employed non-standard mutagenesis: inversion of side-chain chirality in engineered monomer allo-Ile(A2)-DKP-insulin. Although the analogue retains native structure and stability, its affinity for the insulin receptor is impaired by 50-fold. Thus, whereas insulin's core readily accommodates allo-isoleucine at A2, its activity is exquisitely sensitive to chiral inversion. We propose that the Ile(A2) side-chain inserts within a chiral pocket of the receptor as part of insulin's hidden functional surface.

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

1KMF is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

Chiral mutagenesis of insulin's hidden receptor-binding surface: structure of an allo-isoleucine(A2) analogue., Xu B, Hua QX, Nakagawa SH, Jia W, Chu YC, Katsoyannis PG, Weiss MA, J Mol Biol. 2002 Feb 22;316(3):435-41. PMID:11866509

Page seeded by OCA on Thu Mar 20 12:19:22 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1kmf"
Personal tools