8api

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spinqualitylabelsall models 8api, resolution 3.1Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

THE S VARIANT OF HUMAN ALPHA1-ANTITRYPSIN, STRUCTURE AND IMPLICATIONS FOR FUNCTION AND METABOLISM

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 CYS as ligand. This structure superseeds 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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