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.


3bxq

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px <!-- The line below this paragraph, containing "STRUCTURE_3bxq", creates the "Structure Box" on the page. You may change the PDB parameter (which sets the PD...)
Line 1: Line 1:
-
[[Image:3bxq.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:3bxq.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_3bxq| PDB=3bxq | SCENE= }}
{{STRUCTURE_3bxq| PDB=3bxq | SCENE= }}
-
'''The structure of a mutant insulin uncouples receptor binding from protein allostery. An electrostatic block to the TR transition'''
+
===The structure of a mutant insulin uncouples receptor binding from protein allostery. An electrostatic block to the TR transition===
-
==Overview==
+
<!--
-
Single-chain insulin (SCI) analogs provide insight into the inter-relation of hormone structure, function, and dynamics. Although compatible with wild-type structure, short connecting segments (&lt;3 residues) prevent induced fit upon receptor binding and so are essentially without biological activity. Substantial but incomplete activity can be regained with increasing linker length. Here, we describe the design, structure, and function of a single-chain insulin analog (SCI-57) containing a 6-residue linker (GGGPRR). Native receptor-binding affinity (130 +/- 8% relative to the wild type) is achieved as hindrance by the linker is offset by favorable substitutions in the insulin moiety. The thermodynamic stability of SCI-57 is markedly increased (DeltaDeltaG(u) = 0.7 +/- 0.1 kcal/mol relative to the corresponding two-chain analog and 1.9 +/- 0.1 kcal/mol relative to wild-type insulin). Analysis of inter-residue nuclear Overhauser effects demonstrates that a native-like fold is maintained in solution. Surprisingly, the glycine-rich connecting segment folds against the insulin moiety: its central Pro contacts Val(A3) at the edge of the hydrophobic core, whereas the final Arg extends the A1-A8 alpha-helix. Comparison between SCI-57 and its parent two-chain analog reveals striking enhancement of multiple native-like nuclear Overhauser effects within the tethered protein. These contacts are consistent with wild-type crystal structures but are ordinarily attenuated in NMR spectra of two-chain analogs, presumably due to conformational fluctuations. Linker-specific damping of fluctuations provides evidence for the intrinsic flexibility of an insulin monomer. In addition to their biophysical interest, ultrastable SCIs may enhance the safety and efficacy of insulin replacement therapy in the developing world.
+
The line below this paragraph, {{ABSTRACT_PUBMED_18332129}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 18332129 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_18332129}}
==About this Structure==
==About this Structure==
Line 31: Line 35:
[[Category: Receptor binding]]
[[Category: Receptor binding]]
[[Category: Tr transition]]
[[Category: Tr transition]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu May 22 21:52:40 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:14:21 2008''

Revision as of 04:14, 28 July 2008

Image:3bxq.png

Template:STRUCTURE 3bxq

The structure of a mutant insulin uncouples receptor binding from protein allostery. An electrostatic block to the TR transition

Template:ABSTRACT PUBMED 18332129

About this Structure

3BXQ is a Protein complex structure. Full crystallographic information is available from OCA.

Reference

Design of an Active Ultrastable Single-chain Insulin Analog: SYNTHESIS, STRUCTURE, AND THERAPEUTIC IMPLICATIONS., Hua QX, Nakagawa SH, Jia W, Huang K, Phillips NB, Hu SQ, Weiss MA, J Biol Chem. 2008 May 23;283(21):14703-16. Epub 2008 Mar 10. PMID:18332129

Page seeded by OCA on Mon Jul 28 07:14:21 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3bxq"
Personal tools