title: Proton transfer in catalysis and the role of proton shuttles in carbonic anhydrase.
abstract: The undisputed role of His64 in proton transfer during catalysis by carbonic anhydrases in the alpha class has raised questions concerning the details of its mechanism. The highly conserved residues Tyr7, Asn62, and Asn67 in the active-site cavity function to fine tune the properties of proton transfer by human carbonic anhydrase II (HCA II). For example, hydrophobic residues at these positions favor an inward orientation of His64 and a low pK(a) for its imidazole side chain. It appears that the predominant manner in which this fine tuning is achieved in rate constants for proton transfer is through the difference in pK(a) between His64 and the zinc-bound solvent molecule. Other properties of the active-site cavity, such as inward and outward conformers of His64, appear associated with the change in DeltapK(a); however, there is no strong evidence to date that the inward and outward orientations of His64 are in themselves requirements for facile proton transfer in carbonic anhydrase.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610-0267, USA.
authors.forename: Rose L
authors.initials: RL
authors.lastname: Mikulski
authors.forename: David N
authors.initials: DN
authors.lastname: Silverman
mesh_terms: D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D006801:Humans; D011522:Protons
chemical_list: D011522:Protons; D002256:Carbonic Anhydrases
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