1nmv

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{{STRUCTURE_1nmv| PDB=1nmv | SCENE= }}
{{STRUCTURE_1nmv| PDB=1nmv | SCENE= }}
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'''Solution structure of human Pin1'''
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===Solution structure of human Pin1===
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==Overview==
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The peptidyl-prolyl cis/trans isomerase hPin1 is a phosphorylation-dependent regulatory enzyme whose substrates are proteins involved in regulation of cell cycle, transcription, Alzheimer's disease, and cancer pathogenesis. We have determined the solution structure of the two domain protein hPin1-(1-163) and its separately expressed PPIase domain (50-163) (hPin1PPIase) with an root mean square deviation of &lt;0.5 A over backbone atoms using NMR. Domain organization of hPin1 differs from that observed in structures solved by x-ray crystallography. Whereas PPIase and WW domain are tightly packed onto each other and share a common binding interface in crystals, our NMR-based data revealed only weak interaction of both domains at their interface in solution. Interaction between the two domains of full-length hPin1 is absent when the protein is dissected into the catalytic and the WW domain. It indicates that the flexible linker, connecting both domains, promotes binding. By evaluation of NOESY spectra we can show that the alpha1/beta1 loop, which was proposed to undergo a large conformational rearrangement in the absence of sulfate and an Ala-Pro peptide, remained in the closed conformation under these conditions. Dissociation constants of 0.4 and 2.0 mm for sulfate and phosphate ions were measured at 12 degrees C by fluorescence spectroscopy. Binding of sulfate prevents hPin1 aggregation and changes surface charges across the active center and around the reactive and catalytically essential Cys113. In the absence of sulfate and/or reducing agent this residue seems to promote aggregation, as observed in hPin1 solutions in vitro.
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{{ABSTRACT_PUBMED_12721297}}
==About this Structure==
==About this Structure==
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1NMV is a [[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=1NMV OCA].
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1NMV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NMV OCA].
==Reference==
==Reference==
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[[Category: Ppiase domain]]
[[Category: Ppiase domain]]
[[Category: Ww domain group iv]]
[[Category: Ww domain group iv]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:43:31 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 15:38:18 2008''

Revision as of 12:38, 27 July 2008

Template:STRUCTURE 1nmv

Solution structure of human Pin1

Template:ABSTRACT PUBMED 12721297

About this Structure

1NMV is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

Structural analysis of the mitotic regulator hPin1 in solution: insights into domain architecture and substrate binding., Bayer E, Goettsch S, Mueller JW, Griewel B, Guiberman E, Mayr LM, Bayer P, J Biol Chem. 2003 Jul 11;278(28):26183-93. Epub 2003 Apr 29. PMID:12721297

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