1rwe

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[[Image:1rwe.gif|left|200px]]<br /><applet load="1rwe" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1rwe.gif|left|200px]]
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caption="1rwe, resolution 1.80&Aring;" />
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'''Enhancing the activity of insulin at receptor edge: crystal structure and photo-cross-linking of A8 analogues'''<br />
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{{Structure
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|PDB= 1rwe |SIZE=350|CAPTION= <scene name='initialview01'>1rwe</scene>, resolution 1.80&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <scene name='pdbligand=IPH:PHENOL'>IPH</scene>
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|ACTIVITY=
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|GENE=
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}}
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'''Enhancing the activity of insulin at receptor edge: crystal structure and photo-cross-linking of A8 analogues'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1RWE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=IPH:'>IPH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RWE OCA].
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1RWE 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=1RWE OCA].
==Reference==
==Reference==
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Enhancing the activity of insulin at the receptor interface: crystal structure and photo-cross-linking of A8 analogues., Wan Z, Xu B, Huang K, Chu YC, Li B, Nakagawa SH, Qu Y, Hu SQ, Katsoyannis PG, Weiss MA, Biochemistry. 2004 Dec 28;43(51):16119-33. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15610006 15610006]
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Enhancing the activity of insulin at the receptor interface: crystal structure and photo-cross-linking of A8 analogues., Wan Z, Xu B, Huang K, Chu YC, Li B, Nakagawa SH, Qu Y, Hu SQ, Katsoyannis PG, Weiss MA, Biochemistry. 2004 Dec 28;43(51):16119-33. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15610006 15610006]
[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Chu, Y C.]]
[[Category: Chu, Y C.]]
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[[Category: insulin receptor]]
[[Category: insulin receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:55:14 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:57:05 2008''

Revision as of 11:57, 20 March 2008

Image:1rwe.gif


PDB ID 1rwe

Drag the structure with the mouse to rotate
, resolution 1.80Å
Ligands: , and
Coordinates: save as pdb, mmCIF, xml



Enhancing the activity of insulin at receptor edge: crystal structure and photo-cross-linking of A8 analogues


Contents

Overview

The receptor-binding surface of insulin is broadly conserved, reflecting its evolutionary optimization. Neighboring positions nevertheless offer an opportunity to enhance activity, through either transmitted structural changes or introduction of novel contacts. Nonconserved residue A8 is of particular interest as Thr(A8) --> His substitution (a species variant in birds and fish) augments the potency of human insulin. Diverse A8 substitutions are well tolerated, suggesting that the hormone-receptor interface is not tightly packed at this site. To resolve whether enhanced activity is directly or indirectly mediated by the variant A8 side chain, we have determined the crystal structure of His(A8)-insulin and investigated the photo-cross-linking properties of an A8 analogue containing p-azidophenylalanine. The structure, characterized as a T(3)R(3)(f) zinc hexamer at 1.8 A resolution, is essentially identical to that of native insulin. The photoactivatable analogue exhibits efficient cross-linking to the insulin receptor. The site of cross-linking lies within a 14 kDa C-terminal domain of the alpha-subunit. This contact, to our knowledge the first to be demonstrated from the A chain, is inconsistent with a recent model of the hormone-receptor complex derived from electron microscopy. Optimizing the binding interaction of a nonconserved side chain on the surface of insulin may thus enhance its activity.

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

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

Reference

Enhancing the activity of insulin at the receptor interface: crystal structure and photo-cross-linking of A8 analogues., Wan Z, Xu B, Huang K, Chu YC, Li B, Nakagawa SH, Qu Y, Hu SQ, Katsoyannis PG, Weiss MA, Biochemistry. 2004 Dec 28;43(51):16119-33. PMID:15610006

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