2oay: Difference between revisions
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New page: left|200px<br /> <applet load="2oay" size="450" color="white" frame="true" align="right" spinBox="true" caption="2oay, resolution 2.35Å" /> '''Crystal structure o... |
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[[Image:2oay. | [[Image:2oay.jpg|left|200px]]<br /><applet load="2oay" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2oay" size=" | |||
caption="2oay, resolution 2.35Å" /> | caption="2oay, resolution 2.35Å" /> | ||
'''Crystal structure of latent human C1-inhibitor'''<br /> | '''Crystal structure of latent human C1-inhibitor'''<br /> | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
2OAY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 2OAY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OAY OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: latent serpin; rcl insertion]] | [[Category: latent serpin; rcl insertion]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:14:30 2008'' | ||
