7api
From Proteopedia
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|PDB= 7api |SIZE=350|CAPTION= <scene name='initialview01'>7api</scene>, resolution 3.0Å | |PDB= 7api |SIZE=350|CAPTION= <scene name='initialview01'>7api</scene>, resolution 3.0Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CYS:CYSTEINE'>CYS</scene> | + | |LIGAND= <scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=7api FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7api OCA], [http://www.ebi.ac.uk/pdbsum/7api PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=7api RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Emphysema OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107400 107400]], Emphysema-cirrhosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107400 107400]], Hemorrhagic diathesis due to antithrombin Pittsburgh OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107400 107400]], Pulmonary disease, chronic obstructive, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107400 107400]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Loebermann, H.]] | [[Category: Loebermann, H.]] | ||
[[Category: Tokuoka, R.]] | [[Category: Tokuoka, R.]] | ||
| - | [[Category: CYS]] | ||
[[Category: proteinase inhibitor]] | [[Category: proteinase inhibitor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:43:51 2008'' |
Revision as of 02:43, 31 March 2008
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| , resolution 3.0Å | |||||||
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| Ligands: | , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE S VARIANT OF HUMAN ALPHA1-ANTITRYPSIN, STRUCTURE AND IMPLICATIONS FOR FUNCTION AND METABOLISM
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.
About this Structure
7API is a Single protein structure of sequence from [1]. This structure supersedes the now removed PDB entry 5API. 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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