In silico identification of human endopeptidase inhibitor protein, alpha 1-antitrypsin; approach toward colon cancer biomarker identification / Norellina Selamat

Alpha 1-Anti trypsin (AAT) is a major plasma protease inhibitor synthesized in hepatocytes and macrophages. AAT is a globular glycoprotein of molecular weight 52 kilodalton (kD) with the unique chain of 394 amino acids and 3 lateral chains of carbohydrate linked by 3 residues of asparagines. Hepatocyte is the primary source of AAT but other cells including monocytes, macrophages, and lung and intestinal epithelial cell may also synthesis low quantities of the protein. AAT has one active site known as SERPIN profile which is responsible for the anti-protease activity. The absent of AAT leads to destruction of colon and rectum membrane by protease, leaving the colon and rectum vulnerable to cancer development. Absent of AAT can occur through few ways (1) a reduction in the levels of AAT as occurs in AAT heterozygotes; (2) a reduction in the functional levels of AAT as might occur in cigarette smokers; or (3) an increase in the local concentration of proteases such as neutrophil elastase, as might occur in acute inflammatory states. AAT-degrading activity of Matrix Metalloproteinases (MMP) could contribute to tumor progression not only via the inactivation of the proteinase inhibitory activity of AAT, but also via the generation of a biologically active peptide, AAT-C. In silica identification and characterization of AAT provide preliminary information on the structure and function of the protein in human. In addition, comparative modeling is becoming a useful technique in the field of bioinformatics because the knowledge of the of protein structure would be an invaluable aid to understand the details of a particular protein. The predicted secondary-dimensional model may be further used in characterizing the interest protein in wet laboratory. The methods in this study can be used to get more information about biosystem by identifying and characterization of other genes and biomolecules.