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2oay

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{{STRUCTURE_2oay| PDB=2oay | SCENE= }}
{{STRUCTURE_2oay| PDB=2oay | SCENE= }}
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'''Crystal structure of latent human C1-inhibitor'''
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===Crystal structure of latent human C1-inhibitor===
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==Overview==
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C1 inhibitor, a member of the serpin family, is a major down-regulator of inflammatory processes in blood. Genetic deficiency of C1 inhibitor results in hereditary angioedema, a dominantly inheritable, potentially lethal disease. Here we report the first crystal structure of the serpin domain of human C1 inhibitor, representing a previously unreported latent form, which explains functional consequences of several naturally occurring mutations, two of which are discussed in detail. The presented structure displays a novel conformation with a seven-stranded beta-sheet A. The unique conformation of the C-terminal six residues suggests its potential role as a barrier in the active-latent transition. On the basis of surface charge pattern, heparin affinity measurements, and docking of a heparin disaccharide, a heparin binding site is proposed in the contact area of the serpin-proteinase encounter complex. We show how polyanions change the activity of the C1 inhibitor by a novel "sandwich" mechanism, explaining earlier reaction kinetic and mutagenesis studies. These results may help to improve therapeutic C1 inhibitor preparations used in the treatment of hereditary angioedema, organ transplant rejection, and heart attack.
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The line below this paragraph, {{ABSTRACT_PUBMED_17488724}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 17488724 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17488724}}
==About this Structure==
==About this Structure==
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[[Category: Latent serpin]]
[[Category: Latent serpin]]
[[Category: Rcl insertion]]
[[Category: Rcl insertion]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:32:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:44:36 2008''

Revision as of 10:44, 28 July 2008

Image:2oay.png

Template:STRUCTURE 2oay

Crystal structure of latent human C1-inhibitor

Template:ABSTRACT PUBMED 17488724

About this Structure

2OAY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

C1 inhibitor serpin domain structure reveals the likely mechanism of heparin potentiation and conformational disease., Beinrohr L, Harmat V, Dobo J, Lorincz Z, Gal P, Zavodszky P, J Biol Chem. 2007 Jul 20;282(29):21100-9. Epub 2007 May 8. PMID:17488724

Page seeded by OCA on Mon Jul 28 13:44:36 2008

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