The S variant of the human α1-antitrysin with E-264 – V, is responsible for a mild α1-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 Å 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 probobly 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 α1-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 structrual and dynamic properties and compared with the experimental results. There is a significant correlation between experimental and theoretical results in some respects.