8api
From Proteopedia
(New page: 200px<br /> <applet load="8api" size="450" color="white" frame="true" align="right" spinBox="true" caption="8api, resolution 3.1Å" /> '''THE S VARIANT OF HUM...) |
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caption="8api, resolution 3.1Å" /> | caption="8api, resolution 3.1Å" /> | ||
'''THE S VARIANT OF HUMAN ALPHA1-ANTITRYPSIN, STRUCTURE AND IMPLICATIONS FOR FUNCTION AND METABOLISM'''<br /> | '''THE S VARIANT OF HUMAN ALPHA1-ANTITRYPSIN, STRUCTURE AND IMPLICATIONS FOR FUNCTION AND METABOLISM'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The S variant of the human alpha 1-antitrypsin with E-264----V, is | + | The S variant of the human alpha 1-antitrypsin with E-264----V, is responsible for a mild alpha 1-antitrypsin deficiency quite common in the European population. S protein specifically cleaved at the susceptible peptide bond was crystallized and its crystal structure determined and refined to 3.1 A resolution. The S variant crystallizes isomorphous to the normal M variant. The difference Fourier electron density map shows the E----V change as outstanding residual density. In addition, small structural changes of the main polypeptide chain radiate from the site of mutation and affect parts far removed from it. By the mutation, internal hydrogen bonds and salt linkages of E-264 to Y-38 and K-487, respectively, are lost. They cause the far-reaching slight distortions and are probably related to the reduced thermal stability of the S mutant. They may also be responsible for slower folding of the polypeptide chain and the clinical symptoms of alpha 1-antitrypsin deficiency. In a theoretical study by molecular dynamics methods simulations of the M and S proteins were made and the results analysed with respect to structural and dynamic properties and compared with the experimental results. There is a significant correlation between experimental and theoretical results in some respects. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 8API 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 CYS as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | + | 8API 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=CYS:'>CYS</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 6API. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8API OCA]. |
==Reference== | ==Reference== | ||
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[[Category: proteinase inhibitor]] | [[Category: proteinase inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:17:44 2008'' |
Revision as of 17:17, 21 February 2008
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THE S VARIANT OF HUMAN ALPHA1-ANTITRYPSIN, STRUCTURE AND IMPLICATIONS FOR FUNCTION AND METABOLISM
Contents |
Overview
The S variant of the human alpha 1-antitrypsin with E-264----V, is responsible for a mild alpha 1-antitrypsin deficiency quite common in the European population. S protein specifically cleaved at the susceptible peptide bond was crystallized and its crystal structure determined and refined to 3.1 A resolution. The S variant crystallizes isomorphous to the normal M variant. The difference Fourier electron density map shows the E----V change as outstanding residual density. In addition, small structural changes of the main polypeptide chain radiate from the site of mutation and affect parts far removed from it. By the mutation, internal hydrogen bonds and salt linkages of E-264 to Y-38 and K-487, respectively, are lost. They cause the far-reaching slight distortions and are probably related to the reduced thermal stability of the S mutant. They may also be responsible for slower folding of the polypeptide chain and the clinical symptoms of alpha 1-antitrypsin deficiency. In a theoretical study by molecular dynamics methods simulations of the M and S proteins were made and the results analysed with respect to structural and dynamic properties and compared with the experimental results. There is a significant correlation between experimental and theoretical results in some respects.
Disease
Known diseases associated with this structure: Emphysema OMIM:[107400], Emphysema-cirrhosis OMIM:[107400], Hemorrhagic diathesis due to antithrombin Pittsburgh OMIM:[107400], Pulmonary disease, chronic obstructive, susceptibility to OMIM:[107400]
About this Structure
8API is a Single protein structure of sequence from Homo sapiens with as ligand. This structure supersedes the now removed PDB entry 6API. Full crystallographic information is available from OCA.
Reference
The S variant of human alpha 1-antitrypsin, structure and implications for function and metabolism., Engh R, Lobermann H, Schneider M, Wiegand G, Huber R, Laurell CB, Protein Eng. 1989 Mar;2(6):407-15. PMID:2785270
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