MTH1880 is a hypothetical protein derived from Methanobacterium thermoautotrophicum, thermophilic methanogen. The solution structure determined by NMR spectroscopy showed that it has a novel $alpha+eta$-fold with a highly acidic ligand binding pocket. Since MTH1880 maintains its ultra-stable structural characteristics at both high temperature and pressure, it has been considered as an excellent model for studying protein folding. To initiate the structural and folding study of MTH1880 in proving its unusual stability, we performed the site directed mutagenesis and biochemical analysis of MTH1880 mutants. Data from circular dichroism and NMR spectroscopy suggest that the point mutations perturbed the structural stability of protein even though the secondary structure is retained. This study will provide the useful information in understanding the role of participating residues during folding-unfolding process and our result will be used in designing further folding experiments for hyper-thermopile proteins like MTH1880.