1tgr
From Proteopedia
(New page: 200px<br /> <applet load="1tgr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tgr, resolution 1.42Å" /> '''Crystal Structure o...) |
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| - | [[Image:1tgr.gif|left|200px]]<br /> | + | [[Image:1tgr.gif|left|200px]]<br /><applet load="1tgr" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1tgr" size=" | + | |
caption="1tgr, resolution 1.42Å" /> | caption="1tgr, resolution 1.42Å" /> | ||
'''Crystal Structure of mini-IGF-1(2)'''<br /> | '''Crystal Structure of mini-IGF-1(2)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Insulin and insulin-like growth factor 1 (IGF-1) share a homologous | + | Insulin and insulin-like growth factor 1 (IGF-1) share a homologous sequence, a similar three-dimensional structure and weakly overlapping biological activity, but IGF-1 folds into two thermodynamically stable disulfide isomers, while insulin folds into one unique stable tertiary structure. This is a very interesting phenomenon in which one amino acid sequence encodes two three-dimensional structures, and its molecular mechanism has remained unclear for a long time. In this study, the crystal structure of mini-IGF-1(2), a disulfide isomer of an artificial analog of IGF-1, was solved by the SAD/SIRAS method using our in-house X-ray source. Evidence was found in the structure showing that the intra-A-chain/domain disulfide bond of some molecules was broken; thus, it was proposed that disulfide isomerization begins with the breakdown of this disulfide bond. Furthermore, based on the structural comparison of IGF-1 and insulin, a new assumption was made that in insulin the several hydrogen bonds formed between the N-terminal region of the B-chain and the intra-A-chain disulfide region of the A-chain are the main reason for the stability of the intra-A-chain disulfide bond and for the prevention of disulfide isomerization, while Phe B1 and His B5 are very important for the formation of these hydrogen bonds. Moreover, the receptor binding property of IGF-1 was analyzed in detail based on the structural comparison of mini-IGF-1(2), native IGF-1, and small mini-IGF-1. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TGR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1TGR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=1TGR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Chang, W | + | [[Category: Chang, W R.]] |
| - | [[Category: Liang, D | + | [[Category: Liang, D C.]] |
| - | [[Category: Yun, C | + | [[Category: Yun, C H.]] |
[[Category: disulfide isomerization]] | [[Category: disulfide isomerization]] | ||
[[Category: igf-1]] | [[Category: igf-1]] | ||
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[[Category: recepter binding]] | [[Category: recepter binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:13:21 2008'' |
Revision as of 13:13, 21 February 2008
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Crystal Structure of mini-IGF-1(2)
Contents |
Overview
Insulin and insulin-like growth factor 1 (IGF-1) share a homologous sequence, a similar three-dimensional structure and weakly overlapping biological activity, but IGF-1 folds into two thermodynamically stable disulfide isomers, while insulin folds into one unique stable tertiary structure. This is a very interesting phenomenon in which one amino acid sequence encodes two three-dimensional structures, and its molecular mechanism has remained unclear for a long time. In this study, the crystal structure of mini-IGF-1(2), a disulfide isomer of an artificial analog of IGF-1, was solved by the SAD/SIRAS method using our in-house X-ray source. Evidence was found in the structure showing that the intra-A-chain/domain disulfide bond of some molecules was broken; thus, it was proposed that disulfide isomerization begins with the breakdown of this disulfide bond. Furthermore, based on the structural comparison of IGF-1 and insulin, a new assumption was made that in insulin the several hydrogen bonds formed between the N-terminal region of the B-chain and the intra-A-chain disulfide region of the A-chain are the main reason for the stability of the intra-A-chain disulfide bond and for the prevention of disulfide isomerization, while Phe B1 and His B5 are very important for the formation of these hydrogen bonds. Moreover, the receptor binding property of IGF-1 was analyzed in detail based on the structural comparison of mini-IGF-1(2), native IGF-1, and small mini-IGF-1.
Disease
Known disease associated with this structure: Growth retardation with deafness and mental retardation due to IGF1 deficiency OMIM:[147440]
About this Structure
1TGR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
1.42A crystal structure of mini-IGF-1(2): an analysis of the disulfide isomerization property and receptor binding property of IGF-1 based on the three-dimensional structure., Yun CH, Tang YH, Feng YM, An XM, Chang WR, Liang DC, Biochem Biophys Res Commun. 2005 Jan 7;326(1):52-9. PMID:15567151
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