9API: The S Variant Of Human Alpha1-Antitrypsin, Structure And Implications For Function And Metabolism

Citation:
Abstract
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.
PDB ID: 9APIDownload
MMDB ID: 54876
PDB Deposition Date: 1988/9/8
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 9API: dimeric; determined by author
Molecular Components in 9API
Label Count Molecule
Proteins (2 molecules)
1
Alpha 1-antitrypsin(Gene symbol: SERPINA1)
Molecule annotation
1
Alpha 1-antitrypsin(Gene symbol: SERPINA1)
Molecule annotation
Chemicals (11 molecules)
1
7
2
3
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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