title: Modeling the structure and proton transfer pathways of the mutant His-107-Tyr of human carbonic anhydrase II.
abstract: We present molecular modeling of the structure and possible proton transfer pathways from the surface of the protein to the zinc-bound water molecule in the active site of the mutant His-107-Tyr of human carbonic anhydrase II (HCAII). No high-resolution structure or crystal structure is available till now for this particular mutant due to its lack of stability at physiological temperature. Our analysis utilizes as starting point a series of structures derived from high-resolution crystal structure of the wild type protein. While many of the structures investigated do not reveal a complete path between the zinc bound water and His-64, several others do indicate the presence of a transient connection even when His-64 is present in its outward conformation. Mutation at the residue 107 also reveals the formation of a new path into the active site. Competing contributions from His-64 sidechain rotation from its outward conformation are also evaluated in terms of optimal path analysis. No indication of a lower catalytic efficiency of the mutant is evident from our results under the condition of thermal stability of the mutant.
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Kharagpur, 721302, India.
authors.forename: Puspita
authors.initials: P
authors.lastname: Halder
authors.forename: Srabani
authors.initials: S
authors.lastname: Taraphder
mesh_terms: D024402:Carbonic Anhydrase II / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D006639:Histidine / Q000235:genetics*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011522:Protons; D012399:Rotation; D014443:Tyrosine / Q000235:genetics*; D014867:Water / Q000737:chemistry
chemical_list: D050505:Mutant Proteins; D011522:Protons; D014867:Water; D014443:Tyrosine; D006639:Histidine; D024402:Carbonic Anhydrase II