title: Impact of the 237th residue on the folding of human carbonic anhydrase II.
abstract: The deficiency of human carbonic anhydrase II (HCAII) has been recognized to be associated with a disease called CAII deficiency syndrome (CADS). Among the many mutations, the P237H mutation has been characterized to lead to a significant decrease in the activity of the enzyme and in the Gibbs free energy of folding. However, sequence alignment indicated that the 237th residue of CAII is not fully conserved across all species. The FoldX theoretical calculations suggested that this residue did not significantly contribute to the overall folding of HCAII, since all mutants had small ΔΔG values (around 1 kcal/mol). The experimental determination indicated that at least three mutations affect HCAII folding significantly and the P237H mutation was the most deleterious one, suggesting that Pro237 was important to HCAII folding. The discrepancy between theoretical and experimental results suggested that caution should be taken when using the prediction methods to evaluate the details of disease-related mutations.
authors.affiliation: Key Laboratory of Bio-Resources and Eco-Environment of MOE, College of Life Science, Sichuan University, Chengdu 610064, China; E-Mail: wmj213@gmail.com.
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Yan
mesh_terms: D000595:Amino Acid Sequence; D024402:Carbonic Anhydrase II / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D016297:Mutagenesis, Site-Directed; D017510:Protein Folding; D055550:Protein Stability; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D024402:Carbonic Anhydrase II